Nano Research Nano Res DOI 10.1007/s12274‐014‐0409‐z 1
“Green pathway” different from simple diffusion in soft
matter: Fast molecule transport within micro/nanoscaled
multiphase porous system
Feng Jiantao1,3, Wang Fang2, Han Xinxiao1, Ao Zhuo1, Sun Quanmei1,3, Hua Wenda1, Chen Peipei1, Jing
Tianwei4, Li Hongyi1,2 (), Han Dong1 ()
Nano Res., Just Accepted Manuscript • DOI: 10.1007/s12274-014-0409-z
http://www.thenanoresearch.com on January 7, 2014
© Tsinghua University Press 2014
Just Accepted This is a “Just Accepted” manuscript, which has been examined by the peer‐review process and has been accepted for publication. A “Just Accepted” manuscript is published online shortly after its acceptance, which is prior to technical editing and formatting and author proofing. Tsinghua University Press (TUP) provides “Just Accepted” as an optional and free service which allows authors to make their results available to the research community as soon as possible after acceptance. After a manuscript has been technically edited and formatted, it will be removed from the “Just Accepted” Web site and published as an ASAP article. Please note that technical editing may introduce minor changes to the manuscript text and/or graphics which may affect the content, and all legal disclaimers that apply to the journal pertain. In no event shall TUP be held responsible for errors or consequences arising from the use of any information contained in these “Just Accepted” manuscripts. To cite this manuscript please use its Digital Object Identifier (DOI®), which is identical for all formats of publication. TABLE OF CONTENTS (TOC)
“Green pathway” different from simple diffusion in
soft
matter:
Fast
molecule
transport
within
micro/nanoscaled multiphase porous system
Feng Jiantao1,3#, Wang Fang2#, Han Xinxiao1#, Ao Zhuo1#,
Sun Quanmei1,3, Hua Wenda1, Chen Peipei1, Jing
Tianwei4, Li Hongyi1,2*, Han Dong1*
1
National Center for Nanoscience and Technology,
Beijing 100190, People’s Republic of China
2
Cardiology Division, Beijing Hospital of the Ministry of
Health, Beijing 100730, People’s Republic of China
3
Department of Chemistry, Tsinghua University, Beijing
The nanoconfined multiphase effect mediates fast molecule transport
100084, China
within micro/nanoscaled multiphase porous mediums, such as most
4
living tissues and components.
Nano Science Solution Division, Agilent Technologies
Inc, Chandler, Arizona 85226, USA
#
These authors contributed equally to this work.
1
Nano Res DOI (automatically inserted by the publisher) Research Article “Green pathway” different from simple diffusion in soft matter:
Fast molecule transport within micro/nanoscaled multiphase
porous system
Feng Jiantao1,3#, Wang Fang2#, Han Xinxiao1#, Ao Zhuo1#, Sun Quanmei1,3, Hua Wenda1, Chen Peipei1, Jing
Tianwei4, Li Hongyi1,2*(), Han Dong1*()
1
National Center for Nanoscience and Technology, Beijing 100190, People’s Republic of China
2
Cardiology Division, Beijing Hospital of the Ministry of Health, Beijing 100730, People’s Republic of China
3
Department of Chemistry, Tsinghua University, Beijing 100084, China
4
Nano Science Solution Division, Agilent Technologies Inc, Chandler, Arizona 85226, USA
#
These authors contributed equally to this work.
Received: day month year / Revised: day month year / Accepted: day month year (automatically inserted by the publisher)
© Tsinghua University Press and Springer-Verlag Berlin Heidelberg 2011
ABSTRACT Soft matter has now attracted extensive attention due to its special physical/chemical properties and holds great promise in many applications. However, detailed understanding of both complex fluid and mass transport in soft matter, especially in hierarchical porous mediums of biological tissues, still remains to be huge challenge. Herein, inspired by fast tracer transport in loose connective tissues of living systems, we observed an interesting phenomenon of fast molecule transport in situ in an artificial hierarchical multiphase porous medium (i.e., micrometer scale hydrophobic fiber network filled with nanometer scale hydrophilic porous medium), which was simply fabricated through electrospinning technology and polymerization. The transportation speed of molecules in micrometer fiber network is larger than simple diffusion in nanometer medium, better descripted by Fick’s law. We further proved that the phenomenon was based on nanoconfined air/water/solid interface around micrometer hydrophobic fibers. We focus on the influential factors referring to SA, (confined multiphase area around microfibers) and Ng (connectivity node degree of the skeletal portion in nanometer hydrogel medium). Next, a quantitative parameter, VTCM (transport chance mean‐value), was introduced to describe the molecule transport capability of the fiber network within hierarchical multiphase porous systems. These fundamental advances can be applied de novo to understand the process of so‐called simple diffusion in biological systems, and even to re‐describe many living molecule events in biologically nanoconfined spaces. KEYWORDS Soft matter, loose connective tissue, hierarchical multiphase porous medium, mass transport ————————————
Address correspondence to Han Dong, email: [email protected] ; Li Hongyi, email: [email protected];
2
1 Introduction may serve as the “Green Pathway” for fluorescein Soft matter, which is the focus of a novel sodium (FS) transportation when the tracer cross‐discipline science, has attracted far more molecules were injected into subcutaneous LCTs attention due to its important industrial applications near the veins of lower extremities [6]. Histological and biomedical possibilities [1]. Soft matter is examinations and magnetic imaging confirmed the defined as systems whose physical and mechanical visualized pathway, which was first found under an properties are comparable to thermal energy at room anatomical lens. Tracer transport is also involved in temperature, and thus are easily deformed by several parts of body, like the tunica externa of thermal forces; examples include polymers, colloids, venous trees, segments of the small intestines, and foams, droplets in the form of suspensions, liquid partial pulmonary veins, and can result in pericardial crystals, and gels. Controlled by only coarse effusion which is distinguished from conventional macroscopic variables, such as temperature and vascular concentrations, the architectural microstructures of researchers also found that soluble tracers initially soft matter are self‐assembled spontaneously at spread diffusely through the brain parenchyma and micrometer and nanometer scales. As a typical kind later drained out of the brain along basement of soft matter, a multiphase porous medium contains membranes of capillaries and arteries [7]. However, skeletal portions and porous structures that are filled no perivascular drainage was observed when with fluids, including liquids and gases. Based on dextran was injected into mouse brains following their subset of liquid and gas components, complex cardiac arrest. circulations. Coincidentally, other fluids are contained to display non‐Newtonian In general, in vivo transport, especially long‐range rheology of a soft matter system, which may detain transport, always depends on a channel, such as fluid flow through/within porous medium [2, 3]. blood vessels for blood cell transport, and iron From a more general point of view, there are many channels for molecule transport. Herein, the question examples of soft matter that fit the description of is whether there exists a special channel that serves porous systems, including lipid membranes, as a “green pathway”, or whether there is another cytoskeletal protein gels, cell suspensions, and many mechanism based on such a confined space in a other biological systems [4]. In particular, loose micro/nanoscaled multiphase porous system within connective tissues (LCTs) are pliable, mesh‐like LCTs. Accordingly, in the present study that was tissues with a fluid matrix that can be considered as inspired by the hierarchical structures in LCTs, a typical multiphase porous system of soft matter, fabrication of a micro/nanoscaled multiphase porous and can be found in tissue sections from almost system was carried out. The dynamic process of every part of the body. Composed of randomly fluorescent tracer transportation is then addressed in arranged spaces of muscles, tendons, and other tissues [5]. As an artificially porous system. 2 Experimental 2.1 Animal experiment and observation 100‐150 L clinical FS (2% in physiological saline a result, LCTs comprising of fibril bundles (at a solution) was subcutaneously injected into the micrometer scale) and filled with a gel‐like matrix (at upstream site of the perivenous LCTs pathways in protein fibers within abundant extracellular spaces, LCTs are present in blood vessels and nerves, and even penetrate into the small a nanometer scale) constitute the hierarchical porous experimental rabbits. Incisions were made to form a medium to hold organs in place and attach epithelial flap revealing the Great Saphenous Vein (GSV) or tissue to other underlying tissues. Small Saphenous Vein (SSV) under the facial plane In a previous interesting finding, perivenous LCTs on the level of thighs. Photos of LCTs pathways in 3
experimental rats, the same process was performed, 2.3 Time‐series imaging of fluorescent molecule transport The PCL fiber‐PA complex was transferred onto but with no incision. The animals’ care was in the sample stage of fluorescence microscopy (Nikon) accordance with institutional guidelines. The study equipped with DG‐4 (Sutter Instrument). Images protocol was approved by the animal ethics from the CCD were acquired using software the opened planes were taken dynamically by stereomicroscope after injection. As for the committee of the Institute of People’s Hospital of Peking University (No.201170). Anesthesia MetaMorph 7.0. After the addition of 10 L 2% sodium fluorescein solution, the changes in was florescent intensity were recorded at the position of administered intravenously before each of the hydrogel and the hydrogel‐PCL complex in 15 s following experiments. The tracer solution was intervals for 10 min. (pentobarbital at 25‐30 mg/kg/hour) injected subcutaneously and contained 2% lidocaine 2.4 SEM and TEM imaging (accounting for one third of the total volume) for Under anesthesia, a piece of saphenous venous local anesthesia. Each subject was sacrificed via an of the rabbit was separated from the body and overdose of pentobarbital. The wounds in the washed three times with PBS. After fixation in 2.5% animals’ bodies were then disinfected and sutured glutaraldehyde overnight, vessel samples were after experiments. All animals recovered normally dehydrated through graded ethanol solutions of in two weeks. 30%, 50%, 70%, 85%, 95%, 100%, for 10 min each. 2.2 Fabrication of PCL fiber‐PA complex Polycaprolactone (PCL) (Mw 70000–90000, Sigma) was dissolved at a concentration of 12.5% (wt %) in 4/1 (v/v) dimethylformamide (DMF) and dichloromethane (DCM) mixture. During the electrospinning process, the polymer solution was fed at 2 mL h‐1 using a syringe needle (inner diameter of 0.7 mm) under a voltage of 15 kV. The distance between the tip of the needle and the collector was fixed at 20 cm. Samples were collected for 15 min and cut into pieces of 1 cm by 0.3 cm. Uncross‐linked polyacrylamide (PA) solution was prepared by dissolving the acrylamide (Amresco) and bis‐acrylamide (Sigma) into pure water at a concentration of 3% (wt %) and 0.06% (wt %). A piece of the electrospun sample was immersed into the hydrogel solution before polymerization. After introducing the initiators ammonium persulfate (APS) (0.3 v/v %) and N,N,Nʹ,Nʹ‐Tetramethylethylenediamine (TEMED) (0.12 v/v %), 500 L hydrogel solutions were transferred into a confocal petri dish together with the immersed electrospun fibers. A coverslip was placed on the sample for polymerization and prevented evaporation of water within the PA medium. A gap at one side of the coverslip was reserved to later inject FS. Finally, samples were dried by critical point drying and imaged by an environmental scanning electronic microscope (Quanta 200) under low‐vacuum mode. After fixation in 2.5% (v/v %) glutaraldehyde then 1% (wt %) osmium tetroxide for 3 h, respectively, the PCL fiber‐PA complex was dehydrated using the above methods. Acetone replacement was performed three times and the sample was embedded with resin in an incubator for drying at following conditions: 30℃ for 12 h, 35℃for 5 h，37℃ for 12 h，40℃ for 5 h，45℃ for 12 h，47℃ for 5 h，50℃ for 5 h，55℃ for 5 h, and 60℃ for 24 h. Samples were then sectioned and stained with uranyl acetate and lead citrate. Finally imaging was performed using a transmission electron microscope (Hitachi, H‐7500). 2.5 Data Analysis Analysis of the florescent data was performed with the software Origin 8.5. 4
3 Results and discussion In order to acquire high resolution imaging of LCTs structures at micro/nanoscales, the experiment on fluorescent molecule transport through LCTs pathway in rabbits was performed. As shown in Fig. 1, after injection of 2% FS solution subcutaneously at the end of lower limb, the Figure 1 a: Bright field imaging of a saphenous vein of the rabbit by a stereomicroscope. A plastic slice is placed just under the vein,
serving as a foil to clearly show the clear-cut edge of the vein. The arrow points to the perivenous tissues around the vein; b: Fluorescent
image of the same area as (a). FS only appears within perivenous tissues (arrows) rather than blood vessel. Bar is 3000 μm; c:
Fluorescent photo of the tracer diffusion just under abdominal skin of the mouse; Interesting diffusion lines (arrows) are clearly found.
Most of them are easier to run forward to proximal part of body. d: Low vacuum SEM imaging of the perivenous tissues. Bar is 15 μm.
tracer molecule (green color in Fig. 1b) was quickly found in perivenous tissues around the saphenous vein, where a pathway seemed to be constituted directly to proximal part of the vein. We also directly observed this phenomenon from the body surface of rats due to their semitransparent skin. 2% FS solution was also injected subcutaneously at both the abdominal region and terminal region of the four limbs. As shown in Fig. 1c, tracer lines appeared in the abdominal region just under the skin, where no visible vessels were located. Most of the tracer lines were easier to run forward to the proximal part of body. This phenomenon was not found in animal extremities, possibly due to less LCTs under the skin in comparison with abdominal region. All the phenomena mentioned above confirmed that LCTs may help molecule transport by means of an alternative pathway other than through vasculature. The LCTs were then removed from animals and observed by low vacuum SEM. High resolution images showed that micrometer‐wide fibril bundles ran in random directions and constituted a cross‐link network, each of which consisted of numerous closely packed rows of nanometer fibrils. Mesh‐like structures filled the pore space among bundles of fibrils (see Fig. 1d). All of these constituted a micro/nanometer hierarchical profile with nanoconfined space. 5
Figure 2 Sketch diagram of model experiment process. PCL fiber-PA complex was fabricated by introducing the electrospinning fiber
film into the uncross-linked PA solution in recess of a confocal dish, which facilitated the subsequent fluorescent imaging. After
polymerization was over, the network of PCL fibers was firmly embedded in PA. Then PCL fiber-PA complex was transferred on the
sample stage of fluorescence microscopy while adding 10 l FS solution from one side of the PCL fiber-PA complex.
Inspired by this phenomenon, we utilized of polycaprolactone (PCL) fibers to mimic these electrospinning technology to fabricate the network Figure 3 a: Low vacuum SEM imaging of three interlaced PCL fibers (black arrows) removed from a PCL fiber-PA complex. PA
medium (chartreuse arrows) firmly fills in the pores among these fibers. Bar is 15 μm; b: High resolution TEM image of a
cross-section of PCL fibers surrounded with PA medium. Both nanoconfined air/water/solid interfaces around PCL fibers (white
arrows) and a continuous interface between two well-knit PCL fibers (Orange arrows) are easily distinguishable from PA medium
with nanoconfined water pores. Bar is 1000 nm; c: Fluorescence image of PCL fiber-PA complex when FS solution just comes into
contact with the PCL fiber network; d: Fluorescent image of only PA medium on the same latitude as c. Bars in c and d are 50 μm.
microscaled bundles of fibrils within LCTs. As fiber‐PA complex at the bottom of the confocal dish, shown in Fig. 2, we introduced the thin fiber film of which facilitated the subsequent fluorescent PCL into the uncross‐linked polyacrylamide (PA) imaging. After polymerization, the network of PCL solution in the recess, then fabricating the PCL fibers was firmly embedded in PA medium, which 6
was highly water‐absorbent, forming a soft gel successfully addressed as a model, in which when hydrated. A multiphase porous medium with bioinspired hierarchical structures was then Figure 4 Fluorescence intensity changes vs time during the first 400 s. a: Fluorescence intensity changes on the PCL fiber within PCL
fiber-PA complex. D, E, F, G and H represent 5 longitudinally aligned positions in direction of fluorescent propagation respectively.
D was close to the initial position of FS. b: Fluorescence intensity gradients between position D and H, c: Fluorescence intensity
changes in only PA medium adjacent to the PCL fiber-PA complex. K，L，M，N，O represented 5 longitudinally aligned positions in
direction of fluorescent propagation respectively, K was close to the initial position of FS. d: Fluorescence intensity gradients
between position K and O. D and K, E and L, F and M, G and N, H and O located at the positions of the same latitude, respectively.
Distance between each adjacent position was 20 m.
nanoscaled multiphase PA medium filled into the rehabilitation of vessel and nerve injury, instead of microscaled pore space among PCL fibrils. Since the native LCTs. High resolution imaging from focus of this study was just on the structure itself low‐vacuum SEM provided the most convincing rather than the chemical composition, PCL was evident that PCL fibers (black arrows) crossed each therefore selected as the candidate polymer to other and PA medium (chartreuse arrows) filled in underline the hydrophobic aspect of fibrils within their surrounding spaces (see Fig. 3a). In the TEM LCTs [8]. PCL is easily degraded by hydrolysis of its imaging (Fig. 3b), an air/water/solid interface (white ester linkages in physiological conditions and has arrows) between PCL and PA medium was clearly therefore received a great deal of attention for use observed around the surface of each PCL fibers. as an implantable biomaterial. In particular, it is Furthermore, the contact point between two especially interesting for the preparation of adjacent PCL fibers constituted a continuous long‐term implantable devices, owing to its even three‐phase interface (orange arrows) between PCL slower degradation in comparison to polylactide. fibers and PA medium. Prospectively, the bioinspired multiphase porous Subsequently, we injected 10 l FS from the gap of medium may tissue‐repaired be introduced material to as a new the PCL fiber‐PA complex, as shown in Fig. 2d. In promote the the beginning phase, FS diffused in the 7
polyacrylamide hydrogel in a similar manner as the According to Fick’s second law, how diffusion spreading‐out of the solute in pure water, but at a causes the concentration to change with time is slow rate. Amazingly, once FS came into contact addressed by the following equation: with PCL fibers, the whole fiber network was immediately stained. More interestingly, at each contact point among PCL fibers, fluorescent C
 2C
D 2
t
x intensity distinctly peaked (see Fig. 3c). Fig. 3c and Where C is the concentration at point x; t is time; 3d show the fluorescent imaging of the PCL fiber and D is the diffusion coefficient. In the PA medium, network and PA medium on the same latitude, the change of FS diffusion with time is consistent respectively. Comparisons of fluorescence intensity with the rules of Fick’s second law (as shown in Fig. of five longitudinally aligned positions in the 4c and 4d). But around the PCL fibers, FS quickly direction of fluorescent propagation on PCL fibers reaches saturation station, which is different from and in the only PA hydrogel adjacent to the PCL the gradual diffusion process within PA medium fiber‐PA complex were analyzed. D and K, E and L, (compare Fig. 4b and 4d). This proves that a high F and M, G and N, H and O located at the positions efficiency pathway exists around the fibers. Thus, of the same latitude in the PA hydrogel and on PCL how do the fibers remove obstacles from the fibers, respectively (Fig. 4a and 4c). Distance multiphase porous medium to constitute a “green between each adjacent position was 20 m. As pathway” around their own surfaces? shown in Fig. 4a (black arrow), fluorescence stain To better answer this question, we need to return almost simultaneously appeared in all of D, E, F, G to the hierarchical structure within this bioinspired and H at the time point of 50 s. The time‐series multiphase porous medium which is mentioned fluorescence intensity gradients between position D above, i.e., micrometer fibers and nanostructure and H (See Fig. 4b) also showed that concentration hydrogel medium. In fact, many natural materials gradients did not obviously change among these exhibit structure on more than one length scale. In fibers after the fluorescence stain appeared. It other words, the structural elements themselves have demonstrated that FS may transport very fast structure. This structural hierarchy can play a major among the fibers. As control, after the time point of part in determining the bulk material properties, 300 s, K, L, M, N and O just began to successively such as physical and mechanical properties. Recently, present the fluorescent evident (See the black arrow more and more researchers agree with the in Fig. 4c). Fig. 4d clearly showed the process. All standpoint that mentioned above indicated that FS may take a materials are of increasing importance because of different delivery way within PCL fiber‐PA complex their potential application in catalysis, separation in comparison to those in only PA medium. In other technology, or bioengineering [10]. Apart from these words, FS spread out in an ultra‐fast speed along applications, we paid closer attention to whether or the fiber network. Herein, the question arises not special molecule events such as transport and relating what is driving the ultra‐fast transport of permeability FS. micro‐/nanoscaled structures in the present case. As we know, Fickʹs laws of diffusion can be used hierarchical are also porous decided polymer by the To better describe the diffusion dynamics of solute to describe why and how the solute appears to through biological structures, the first Fick’s law move gives rise to the following formula [11]: smoothly and systematically from high‐concentration to low‐concentration areas [9]. 8
J  P
C
x rough topography (see Fig. 3). As a result, in comparison with nanoconfined pores of hydrogel, Where J is the flux of solute, and P is the permeability, nanoconfined spaces induced by multiphase an experimentally determined membrane parameter interfaces around the microfibers may have more related with the solid content and the degree of cross‐link pathways to the further extremity of the crosslinking of hydrogel. Herein, it postulates that network through the bulk. Recently, the transport of the biological structure remains homogeneous like a mass and charge in nanoconfined spaces with at least phospholipid bilayer membrane. But in most one dimension smaller than 100 nm enables the heirachical occurrence of novel phenomena that are not micro/nanostructures of porous system, like LCTs, observed in the bulk [14]. For example, water inside two aspects may make a great impact on the hydrophobic carbon nanotubes runs much faster diffusion of particles or gas in the microenvironment. than in the bulk. This transmission of water results The first is nanoconfined spaces within the from the tight hydrogen‐bonding network inside the multiphase hydrogel medium, i.e., nanoscaled pores tube, which ensures that density fluctuations in the filled with water among the skeletal portion, where surrounding bath lead to concerted and rapid complex of motion along the tube axis[15]. Meanwhile, ion multi‐component soft materials that can flow, but mobility in nanoconfined spaces is also much higher that display non‐Newtonian rheology. The high than in the bulk [16]. The asymmetric charges biological systems fluids refer with to the subset resolution TEM imaging of PA medium can depict distribution arising from selective modification along the panoramic view of the water‐hydrogel porous the nanochannel axis dominates the ionic current medium (see Fig. 3b). The particle or gas in such rectification effect [17]. In the case of PCL fibers with complex fluid needs to undergo interactions with not PA medium, both the molecule interactions on only water molecules, but also with liquid / solid hydrophobic surface and the intrinsic diffusion force interfaces. Thus, the diffusion resistance will be far stored in the nanostructure PA medium are deduced greater than its diffusion in water state. In our to mediate the fast and long‐term transport of observation, the diffusion curve of FS within molecules. Recruitment of FS in the intersection of hydrogel (Fig. 4d) showed a very slow transport these fibers clearly indicates that this “green process. From another standpoint, the water phase pathway” really has the ability of transporting inside the nanostructure hydrogel is still a molecules to the further extremities. These continuous medium. As a result, the intrinsic phenomena diffusion force from one side to another side still transport of mass and charge through nanoconfined remained inside the PA medium. spaces is a fundamental process of interest in biology, Another influential aspect on diffusion is the multiphase interface between demonstrate that the controlled physics and chemistry [18]. hydrophobic Similar to the flow in a cross‐link network, we microfiber and hydrophilic nanostructure hydrogel could consider the mass, such as molecule or gas, as mediums, as shown in Fig. 3b. Thus far, much single flow while water serves as the media. evidence has unambiguously confirmed that Although a detailed mechanism of how the nanobubbles or a depletion layer of water exists on a molecule moves along the multiphase interface hydrophobic surface [12, 13]. In our hierarchical case, requires further understanding and exploration, we the nanobubbles or air layer less than 100 could still address the factors affecting the mass nanometers actually assembled on the microfiber transport. Since the microfibers are hydrophobic, surface, constituting a nanoconfined space with water is only trapped into the pores confined by the 9
skeletal portion of the hydrophilic hydrogel transport in soft matter are ubiquitous in nature and medium. Ignoring the complex movement of water have a number of important biological applications. in situ, we deduce that mass transport is directly Herein, in order to determine the mass transport linked to the stability of porous structure and the capability of a fiber network within hierarchical soft number of pores, which is proportional to the matter, we introduce a descriptive parameter, intensity of skeletal portion, and is relative to the transport chance mean‐value (VTCM), which can be elastic modulus G. Then we derive the flux relation calculated as follows: to material parameters: VTCM 
C
J  S A NG
x i  Ni
S
This formula defines the efficiency of solute transportation in the cross‐link network through the Where SA is the specific interface area of the linking points. Ni is the number of linking points at multiphase between the microfibers and the PA the connectivity degree of i, and S is the total medium, and NG represents the structure parameter, multiphase area in the same volume. Here, the connectivity node degree, regarding the mesh‐like surface area is actually the interface of fibers and skeletal portion of hydrogel medium. This is still medium, which means the intrinsic properties of not the whole picture and further study on the the hydrogel medium could also affect VTCM, such as affecting parameters is required. Carefully the topological structure, hardness, type of the inspecting Fig. 4a, we found that the fast hydrogel polymer, etc. From here, we can easily transportation process occurred at the beginning understand and describe the process of mass and resulted in the almost linear increase of solute transport in a micro‐/nanoscale porous system in concentration. Most importantly, the five measuring nature. In living biological systems, LCTs with a typical structure of micro‐/nanoscale porous system are found beneath the dermis layer, underneath the epithelial tissue of all the body systems that have external openings and in the mesentry which is surrounding the intestine. LCTs are also a component of the lamina propria of the digestive and respiratory tracts, the mucous membranes of reproductive and urinary systems, the stroma of glands, the hypodermis of the skin, and so on. It is not difficult to deduce that LCTs undoubtedly serve as sites of mass exchange and reservoirs of water, ions and salts for surrounding tissues. Almost all cells obtain their nutrients (including gas) from and release their wastes into LCTs. In view of these requirements, LCTs not only need high‐performance and fast transportation, but also need relatively low diffusion to keep the appropriate concentration of the mass. A micro‐/nanoscaled multiphase porous system is well positioned to meet its functions. Furthermore, for all parts of a living element, even points spaced along the transporting direction showed almost identical values, which means the transportation along the microfibers is even faster than in pure water. However, the following exponentially increasing step suggests that diffusion occurred from PA medium towards the microfibril surfaces. Obviously, transport or permeability properties of micro‐/nanoscaled multiphase porous media are typically determined by their structure at scales from a few nanometers to a few microns. Besides molecule‐molecule interaction on a hydrophobic surface, the fast and long distance transportation of molecules is also dependent on complex fluids within the subset of multi‐component soft matter. Like a philosophical description in the literature, “soft matter can move in unprecedented ways and confer unprecedented flow properties on fluids” [19]. Together, in situ complex fluids and oversimplified 10
like a single cell and its surrounding matrix, they can be recognized as micro‐/nanostructure multiphase porous system. Does a red blood cell utilize its “green pathway” within its own cytoskeleton network to perform high effective exchange of gas? Does a signal molecule within cell move quickly along the “green pathway” of cytoskeleton network to meet its downstream partner? Does a matrix function as a “green pathway” besides its support system? Can nanoparticles cross over biological tissues by means of this “green pathway”? Many unclear mechanisms in living systems are waiting to be addressed based on this “green pathway” in micro/nanostructure multiphase porous systems of soft matter. 4 Conclusions In our current study, we found that fast molecule transport along a multiphase interface serves as a high‐performance “green pathway” within micro‐/nanoscaled multiphase porous systems of soft matter. VTCM is then introduced to quantitatively describe the mass transport capability of the fiber network within hierarchical soft matter. These advances in our fundamental knowledge of this phenomenon are being applied de novo to understand the so‐called simple diffusion process in biological systems, and even to re‐describe many living molecule events in biologically nanoconfined spaces. It is also promising for developing novel technologies and applications such as bio‐sensing, molecular transport and separation, bioengineering, tissue‐repairing and drug‐delivery in confined environments. Wenda, and Sun Quanmei; Analyzed the data: Feng Jiantao, Han Xinxiao, Chen Peipei and Hua Wenda; Formula description: Ao Zhuo, Han Dong and Jing Tianwei. Wrote the paper: Feng Jiantao, Ao Zhuo, Han Dong and Jing Tianwei. References [1]
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