Interfacing Nanoparticles to Biology
Kimberly Hamad-Schifferli
Biological and Mechanical Engineering, MIT
Nanoscale interfaces
with proteins and
DNA
+
+H
3N
S
S
S
+
S NH3
+ H 3N
f2
f
N+
S
H3 N
f1
H3
N
H3
+
Understanding and
manipulation of particle
heating
Synthesis of nanoparticles with
unique properties
S
+
S NH3
S
NH
+
3
Multifunctional particles
Triggering drug release
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Nanoscale Interfaces to Biology
red blood cell
~5 µm (SEM)
DNA
proteins
nm
Simple
molecules
<1nm
diatom
30 µm
bacteria
1 µm
10-10
10-9
10-8
10-7
10-6
m
10-5
10-4
10-3
10-2
SOI transistor
width 0.12µm
semiconductor
nanocrystal (CdSe)
5nm
Nanometer memory element
1012 bits/cm2 (1Tbit/cm2)
Circuit design
Copper wiring
width 0.2µm
control biological machines
IBM PowerPC 750TM
Microprocessor
7.56mm×8.799mm
6.35×106 transistors
Controlling Biology with Nanoparticles
Making an interface that
preserves biological function
(quantify)
Exploit physical properties of
inorganic nanoparticles
•Heating by fields
•Fluorescence + Magnetic
Target function of biological
molecules and processes
•Multifunctional particles
•Drug Delivery
•Imaging
•Gene expression
Enhancing Antisense Gene Regulation with NPs
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•
Use NPs to enhance antisense by steric blockage
Study conformation of DNA on NP
protein
ribosome
+
AUG
mRNA
protein
protein
antisense strand
(DNA 15-20mer)
antisense strand
with NP
ribosome
~20nm
AUG
AUG
no protein
no protein
~7nm NP with
DNA 14mers
S. Park, K. A. Brown, K. Hamad-Schifferli, Nano Lett., 2004
S. Park and K. Hamad-Schifferli, J. Phys. Chem. C, 2008
K. A. Brown, S. Park, K. Hamad-Schifferli, J. Phys. Chem. C, 2008
K. A. Brown and K. Hamad-Schifferli, in prep, 2008
Characterizing NP-protein Interfaces
NP ligand
positive/negative/neutral
improve/worsen protein folding?
MD simulations
(Wonmuk Hwang, TAMU)
molecular interactions
Labeling site
Sites sensitive to protein stability?
NP material
Different affinity for
different residues?
NP size
effect of curvature on protein folding?
M.-E. Aubin, D. G. Morales, K. Hamad-Schifferli., Nano Lett., 2005
M.-E. Aubin-Tam and K. Hamad-Schifferli., Langmuir, 2005
M.-E. Aubin-Tam, H. Zhou, K. Hamad-Schifferli., Soft Matter, 2008
M.-E. Aubin-Tam and K. Hamad-Schifferli, Biomed Mater, 2008
M.-E. Aubin-Tam, W. Hwang, K. Hamad-Schifferli, in prep, 2008
Nanoparticles as multifunctional therapeutic agents
•
•
•
Inefficient conjugation
Large
Stability and biocompatibility
Carrier for drugs
Imaging (multimodal)
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targeting
Au8-PAMAM particles:
Polyamidoamine dendrimer
• Delivery
• Functionalizable
T1
Au8:
T2
Untreated
•Fluorescence
•MRI
60nM
120nM
~3nm
V. S. Lelyveld, M.G. Shapiro, A.P. Jasanoff, K. Hamad-Schifferli, in prep.