Adv Physiol Educ 41: 260–265, 2017;
doi:10.1152/advan.00100.2016.
HOW WE TEACH
Generalizable Education Research
Validating a conceptual framework for the core concept of “cell-cell
communication”
X Joel Michael,1 Patricia Martinkova,2 Jenny McFarland,3 Ann Wright,4† William Cliff,5 Harold Modell,6
and Mary Pat Wenderoth7
1
Submitted 30 June 2016; accepted in final form 9 March 2017
Michael J, Martinkova P, McFarland J, Wright A, Cliff W,
Modell H, Wenderoth MP. Validating a conceptual framework for
the core concept of “cell-cell communication”. Adv Physiol Educ 41:
260 –265, 2017; doi:10.1152/advan.00100.2016.—We have created
and validated a conceptual framework for the core physiology concept
of “cell-cell communication.” The conceptual framework is composed
of 51 items arranged in a hierarchy that is, in some instances, four
levels deep. We have validated it with input from faculty who teach
at a wide variety of institutional types. All items making up the
framework were deemed essential to moderately important. However,
some of the main ideas were clearly judged to be more important than
others. Furthermore, the lower in the hierarchy an item is, the less
important it is thought to be. Finally, there was no significant difference in the ratings given by faculty at different types of institutions.
conceptual framework; core concept; cell-cell communication; physiology
American biology education have come
from a variety of different directions. The Conceptual Assessment in Biology (CAB) meetings sponsored by the National
Science Foundation (7, 9) sought to promote assessment practices that examined students understanding of the core concepts, as well as testing their retention of the facts.
Somewhat later, the American Association for the Advancement of Science (1) document Vision and Change emphasized
the need for greater attention to student understanding of the
core concepts of biology.
Both calls for reform recognized that a necessary first step to
assessing conceptual understanding is to identify the core
concepts to be understood.
What are the core concepts? A core concept (often referred
to in the education literature as a “big idea”) has been described
by Duschl et al. (3) as “well tested, validated, and absolutely
central to the discipline. Each integrates many different findings and has exceptionally broad explanatory scope. Each is
the source of coherence for many key concepts, principles, and
even other theories in the discipline.”
CALLS FOR REFORM IN
†Deceased 6 August 2016.
Address for reprint requests and other correspondence: J. Michael, 2449
Crawford Ave., Evanston, IL 60201 (e-mail: [email protected]).
260
Participants at the first CAB meeting (7) defined eight core
concepts of biology. We took that list of core concepts and,
with significant input from the physiology teaching community, identified a set of 15 core concepts of physiology and
established the community’s ranking of the importance of these
core concepts (8, 11). The top three core concepts, according to
the faculty surveyed, were homeostasis, cell-cell-communication, and cell membrane.
What is a conceptual framework? A conceptual framework
is a hierarchically organized statement of the ideas that make
up a core concept (5). We have referred to the process of
building a conceptual framework as “unpacking” the core
concept (5).
For our use, we have recognized that a hierarchical conceptual framework will include three kinds of elements: 1) the core
concept; 2) critical components essential for building an accurate model of the core concept; and 3) constituent ideas that are
necessary for understanding each critical component (5).
Unpacking the core concept of homeostasis. We “unpacked”
the core concept of homeostasis, generating a conceptual
framework that describes the hierarchical relationship between
the many ideas that together make up this core concept (5). In
another paper, our laboratory described how teachers can
facilitate student understanding of homeostasis (12).
With the homeostasis conceptual framework in hand, we
wrote a homeostasis concept inventory (a conceptual assessment instrument) and have validated it (6).
Unpacking the cell-cell communication core concept. Here
we describe our unpacking of the core concept of cell-cell
communication and how we validated the conceptual framework through a survey of physiology faculty. This conceptual
framework specifically addresses communications at the level
of the cell and does not address communications processes that
involve cellular networks, tissues, or other communications at
higher levels of biological organization.
In addition to confirming the overall importance of the
components of the cell-cell communication conceptual framework, three hypotheses about the proposed framework and its
items were tested in this study:
Hypothesis 1: The seven main ideas (CC1-CC7; see Table 2)
are not equally important.
1043-4046/17 Copyright © 2017 The American Physiological Society
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Department of Molecular Biophysics and Physiology, Rush Medical College, Chicago, Illinois; 2Institute of Computer
Science, The Czech Academy of Sciences, Prague, Czech Republic; 3Department of Biology, Edmonds Community College,
Lynnwood, Washington; 4Department of Biology, Canisius College, Buffalo, New York; 5Department of Biology, Niagara
University, Niagara, New York; 6Physiology Educational Research Consortium, Seattle, Washington; and 7Department of
Biology, University of Washington, Seattle, Washington
VALIDATED CONCEPTUAL FRAMEWORK FOR COMMUNICATIONS
Hypothesis 2: The importance of an item in the conceptual
framework is determined, in part, by its position in the
hierarchy.
Hypothesis 3: The perceived importance of the items is
dependent on the institution type of the respondent (see
Table 1).
METHODS
Table 1. The types of institutions at which survey
respondents teach
Type of Institution
No. of Respondents
2-yr Community college (2year)
4-yr College granting only BS/BA degrees (4yearBA)
4-yr College granting BA/BA degrees and some graduate
degrees (4year)
Research university (ResU)
Professional school: medical, dental, nursing (Prof)
Total no. of responses analyzed
9
8
10
5
5
37
Forty-three individuals opened the survey, but there were only 37
completed surveys. Respondents teach at wide variety of higher
education institutions (see Table 1).
Statistical analyses. Descriptive statistics (mean and SD) were
calculated for each item in the conceptual framework (see Table 2).
To determine whether our data confirmed or disconfirmed our three
hypotheses (see Introduction), we examined the distribution of the
ratings for the seven main ideas (hypothesis 1), for items of given
level of hierarchy (hypothesis 2), and for responses from different
institution types (hypothesis 3). These distributions were plotted out in
bar graphs (Figs. 1, 2, and 3, respectively).
Furthermore, the data were analyzed using mixed-effects linear
regression models that accounted for correlated responses of respondents. In the full model, the rating was predicted by the item’s main
idea, level of hierarchy, institution type of the respondent, and their
interactions. Simpler models lacked interactions or some of the
predictors. We used Bayesian Information Criteria to select the
optimal model (14). The predictors that were present in the optimal
model were said to significantly influence the rating.
To perform all statistical analyses, we used the freely available
software R version 3.2.4 (13) and its libraries ggplot2 (16), lme4 (2),
and lmerTest (4). The bar graphs were plotted with Excel.
RESULTS
The conceptual framework for the core concept of cell-cell
communication can be seen in Table 2. The ratings for each of
the 51 items were averaged, and the standard deviations were
calculated (see the two right columns of Table 2). In addition,
the proportion of ratings of 5 was also determined and displayed.
Among the 51 items in the conceptual framework, the lowest
rated item had a mean importance score of 3.27 (somewhere
between Important and Moderately Important). The highest
rated item had a score of 4.92 (slightly less than Essential). No
more than two respondents rated any item as Not Important,
and all items were rated as Essential by at least two respondents.
Written comments provided by respondents pointed to one
error in an item and suggested a missing item. There was some
discussion of the difficulty of understanding the wording of
some items. There were also several comments suggesting that
there is not a single right way to construct or write a conceptual
framework (a conclusion with which we strongly agree). Nevertheless, the tenor of the comments suggested we had produced an acceptable description of the ideas making up the
core concept of cell-cell communication.
Based on the ratings and the comments, we conclude that
our respondents found the conceptual framework to have
content and construct validity.
The ratings from all 37 respondents were analyzed to determine whether the data confirm or disconfirm the three hypotheses we proposed (see Introduction).
The seven main ideas (CC1-CC7, Table 2) are not viewed as
being equally important (hypothesis 1). The bar graphs in Fig.
1 show the proportions of ratings of each value for each of the
seven main ideas. Visually it appears that the importance does
vary considerably, e.g., the proportions of ratings with a value
of 5 appear different for the seven main ideas. The regression
analysis supports the conclusion that there is a significant
difference between the rankings of the seven main items (P ⬍
0.001). The same conclusion is supported also when all items
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Development of the cell-cell communication conceptual
framework. Michael et al. (11) provided the initial description of a set
of core concepts in physiology. The set of core concepts was expanded and modified by Michael and McFarland (8) and was validated by several surveys of physiology instructors.
The 2009 paper (11) listed “information” as one of the core
concepts we identified. In Vision and Change (1), one of the five core
concepts of biological literacy referred to is “information flow, exchange, and storage.” Both of these core concepts referenced two
forms of information that operate at two different levels of organization:
1. Information is stored in DNA/RNA and is used within cells to
determine the structure and function of the cell; and
2. Information is exchanged between cells by way of both the
nervous and endocrine systems.
However, feedback from the faculty we surveyed (see below and
Ref. 8) made it clear that these two forms of information needed to be
dealt with separately. The two core concepts that replaced “information” are 1) cell-cell communication and 2) genes to proteins.
Our team created the original unpacking of what we now call
cell-cell communication in 2009 (11). Michael then expanded that
conceptual framework into an “Endocrine Signaling Conceptual
Framework” that he used with his class of first-year medical students.
There were several further rounds of editing, which yielded the
conceptual framework that we used to survey the faculty. This
framework consists of 51 items arranged in a four-level hierarchy that
can be seen in Table 2.
Validating the cell-cell communication conceptual framework. To
establish the content validity of this conceptual framework, a survey
was created (using SurveyMonkey) that asked respondents to rate
each of the 51 items making up the conceptual framework on a
five-point scale:
Essential ( ⫽ 5),
Important ( ⫽ 4),
Moderately Important ( ⫽ 3),
Slightly Important ( ⫽ 2), and
NOT Important ( ⫽ 1).
In addition to rating the items, the respondents were asked to
comment on any changes (additions, deletions, corrections) they
would recommend for the conceptual framework.
Participants. Respondents to previous surveys and individuals who
had participated in past Human Anatomy and Physiology Society
workshops were contacted and asked to participate.
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VALIDATED CONCEPTUAL FRAMEWORK FOR COMMUNICATIONS
Table 2. The cell-cell communication conceptual framework
Core Concept
CC1
CC1.1
CC1.2
CC1.3*
CC1.4*
CC1.5*
CC1.6
CC1.7
CC2
CC2.1
CC2.1.1*
CC2.1.3*
CC2.2*
CC2.3*
CC3
CC3.1
CC3.2
CC3.3
CC3.3.1
CC3.3.2
CC3.4*
CC3.5
CC3.6
CC3.7
CC4
CC4.1
CC4.1.1*
CC4.1.2*
CC4.1.3
CC4.2
CC4.3
CC4.3.1
CC4.3.2
CC4.3.3*
CC4.3.3.1*
CC4.3.3.2*
CC4.3.4*
CC4.3.4.1*
CC4.3.4.2*
SD
%Picking 5
4.92
4.46
4.41
3.95
0.27
0.92
0.79
0.84
92
65
57
27
3.46
0.86
8
3.89
4.14
4.38
4.32
0.80
0.78
0.63
0.81
19
35
46
54
4.14
4.00
0.93
0.81
41
27
3.92
0.88
27
3.51
0.92
14
3.73
1.11
27
3.50
4.84
1.01
0.68
16
92
4.57
4.92
3.97
0.79
0.27
1.08
68
92
38
4.19
4.11
0.98
1.03
53
41
3.95
0.93
30
4.43
0.64
51
4.46
0.76
59
4.49
0.76
62
4.57
4.35
0.68
0.74
68
49
3.84
0.92
27
3.78
0.93
24
3.97
0.88
32
4.16
0.75
35
3.81
4.22
1.02
0.87
32
46
4.32
0.77
49
3.70
3.49
0.95
0.86
22
11
3.57
0.86
11
3.41
3.27
1.03
0.83
14
5
3.32
0.90
11
Continued
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CC2.1.2*
A cell synthesizes and releases a chemical messenger.
A cell synthesizes a messenger molecule.
Messenger molecules can be proteins (or peptides), steroids, or amines.
The rate of release of a messenger from a cell is determined by the “sum” of the
stimuli for release and the stimuli that inhibit release.
Chemical messengers are present at very low concentrations in the blood compared
with other biologically active molecules such as ions and nutrients.
The greater the net stimulus for release, the higher the rate of release of the messenger.
Cells release messengers by exocytosis or diffusion across the cell membrane.
Cells that release messengers can be anywhere in the body.
Transport of messenger molecules is determined by the chemical nature of the
messenger.
The solubility of the molecule determines how it is transported to its target cells.
Protein/peptide and amine messengers are generally water soluble and are transported
in solution.
Steroid messengers are lipid soluble and are transported bound to protein carrier
molecules in the blood.
Some amine messengers are transported bound to transport proteins, and others are
carried in solution.
The extracellular fluid concentration of a messenger molecule depends on the balance
between production/release and elimination of the messenger.
Only the messenger in solution and free to diffuse is biologically active.
The messenger must bind to a receptor protein in or on its target cell to produce a
response.
Each messenger molecule can only bind to a specific receptor molecule.
A cell can only respond to a messenger for which it has receptors.
The solubility of the messenger determines the location of its receptor protein in/on the
target cell.
Water soluble messengers have receptors that are on the target cell membrane.
Lipid soluble messenger have receptors that are inside the target cell, usually in the
nucleus, but, in some cases, in the cytoplasm as well.
The number of receptors for a particular messenger can be relatively small or relative
large and is variable.
There can be more than one type of receptor for the same messenger on different target
cells.
Thus the same messenger can produce different responses in the same type of target
cells wherever they may be in the body.
Cells have a large variety of different receptors, thus enabling them to respond to a
large number of different messengers.
Binding of the messenger molecule to its receptor gives rise to signal transduction.
A single messenger molecule bound to its receptor can activate or alter many more
molecules in the target cell; this is called amplification.
Because target cell response is a multistep process, and amplification occurs at each
step, a single molecule can activate or alter many more molecules; the more steps in
the intracellular signaling process, the greater the amplification can be.
Given that messenger molecules are scarce, if the signal is not amplified, it will have
little physiological effect.
Because the target cell response is a multistep process, there are many points at which
different inputs (other messengers) can modify the outcome/response. This is
referred to as integration.
Because the target cell response is a multistep process, a particular messenger molecule
can have more than one effect in a target cell.
There are two basic mechanisms for transduction, both of which result in amplification.
Binding of a messenger molecule to its receptor can activate a cascade of intracellular
second messengers, which results in altered enzyme activity.
Binding of a messenger molecule to its receptor can alter the processes of translation
and transcription in the cell nucleus, thus altering the concentration of a specific
enzyme in the cell.
The speed of the response of the two systems is different.
The speed of response in a second-messenger system is fast, since second-messenger
molecules are already present in the cell.
The speed of response in transcription and translation systems is slower because new
molecules have to be synthesized.
Persistence of the response to messenger molecules also differs.
In second-messenger systems, the half-life of the molecules that get activated is short,
and the response can be terminated quickly.
In translation/transcription-based systems, the half-life of the molecule (proteins)
produced is longer, so the responses persist longer.
AVG
VALIDATED CONCEPTUAL FRAMEWORK FOR COMMUNICATIONS
263
Table 2.—Continued
Core Concept
CC5
CC5.1
CC5.2*
CC6
CC6.1*
CC6.2*
CC6.3*
CC7
SD
%Picking 5
4.57
4.46
0.82
0.79
73
62
3.92
0.94
30
4.24
4.11
0.79
0.69
46
30
4.03
3.68
4.32
0.75
0.90
0.99
30
16
59
4.16
4.14
4.16
1.05
1.02
1.03
51
49
49
The table includes the number, mean (AVG), and SD (SD) of the ratings (5, Essential; 4, Important; 3, Moderately Important; 2, Slightly Important; 1, NOT
Important) for each item. In addition, we calculated the percentage of all respondents who selected 5 for each item. The data are from 37 respondents. *The items
that might be dropped, since fewer than 30% of the respondents rated them Essential (see the DISCUSSION).
are taken into account and their level of hierarchy is considered
(P ⬍ 0.001).
The importance of an item depends on its position (level) in
the hierarchy (hypothesis 2). A priori this would make sense
since the hierarchy (the outline; see Table 2) has items of
“smaller” application at the lower levels. The bar graphs in Fig.
2 show the proportion of ratings for all items at each of the four
levels in the hierarchy.
As predicted, the lower levels of the framework are viewed
as somewhat less important than the higher levels. The regression analysis clearly confirms this conclusion. Moving to each
lower level, the mean importance of items is reduced by 0.34.
This linear trend is statistically significant (P ⬍ 0.001). However, it is important to bear in mind that the item viewed as
Fig. 1. The proportion of each rating value (5 ⫽ Essential, 4 ⫽ Important,
3 ⫽ Moderately Important, 2 ⫽ Slightly Important, 1 ⫽ NOT Important) for
each of the seven main ideas in the conceptual framework (CC1–CC7) was
determined. There are clear differences in the proportion of 5’s (Essential)
across the set of main ideas, and these differences are statistically significant
(see text).
least important still had a mean importance score of 3.27,
between Important and Moderately Important.
The perceived importance of the items is not dependent on
the institution type of the respondent (hypothesis 3). We have
noted that our respondents teach at a variety of types of
secondary educational institutions (Table 1). Some differences
can be observed among responses coming from different institution types (see Fig. 3). However, we were not able to
statistically confirm any dependence of the rating on the type of
the institution: The sample size in some of the institution types
was very small, and there was also high intraclass variability in
Fig. 2. The number of each of the different ratings for all of the items at each
of the four hierarchical levels were counted, and the proportions were calculated and plotted as bar graphs. Items lower in the hierarchy are thought to be
less important than items higher up (see text).
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CC7.1
CC7.2
CC7.3
Binding of the messenger molecule to its receptor alters cell function.
The response of the target cell is a function of the target cell and not the messenger
molecule. That is to say, the response to a given messenger is determined by the
physiology of the target cell.
Alteration of target cell function is always the result of altering enzyme activity,
whether caused by second-messenger alteration of enzyme activity or by changes in
translation/transcription, causing the appearance of more enzyme molecules.
Termination of a messenger signal is accomplished in several ways.
The messenger signal goes away because the messenger molecule is no longer released
or it is broken down.
The messenger molecule is removed from the receptor.
The receptor ⫹ messenger complex is internalized and ceases to generate a signal.
Some cells can communicate with neighboring cells electrically; they are electrically
coupled.
Electrically coupled cells have gap junctions that span their two membranes.
Current can flow from one cell, when electrically excited, to neighboring cells.
These currents then electrically excite the second cell.
AVG
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VALIDATED CONCEPTUAL FRAMEWORK FOR COMMUNICATIONS
responses. Thus the effect of the institution was not statistically
significant.
DISCUSSION
We have developed and validated a conceptual framework
for the core concept of cell-cell communication. The conceptual framework is large and complex, reflecting the size and
complexity of the phenomena it attempts to describe. This is
not surprising. The concept of cell-to-cell communication extends to every function of the nervous and endocrine systems
in regulation of different body systems, includes synaptic,
paracrine, and endocrine mechanisms of communication, and
integrates molecular, cellular, tissue, organ, and organismal
aspects of communication and regulation across a range of
levels of biological organization.
Of what use is a conceptual framework like this one?
The job of the teacher is to help his or her learners to learn
(10). Concretely, we can describe this task as providing students with opportunities to build, test, and refine their mental
models of whatever phenomena they are asked to master. It is,
of course, essential that students be assessed about what they
have been asked to master.
The participants at the first CAB meeting (7) recognized
that, if you want to assess students’ conceptual understand in
any field, you first had to define what the concepts are. We,
along with a cohort of fellow physiology teachers, have agreed
on the core concepts in physiology (8, 11). We have unpacked
the core concept of homeostasis (5) and have written and
validated a homeostasis concept inventory (6). With a validated conceptual framework for cell-cell communication, it
will now be possible to write and validate a concept inventory
for this core concept.
But conceptual frameworks have other uses as well. The
conceptual framework for cell-cell communication can provide
faculty with a means of explicitly communicating the learning
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Fig. 3. The proportion of the different ratings (for all 51 items) selected by
faculty at five different types of educational institutions was determined and
plotted. See the text for a discussion of the significance of these results. See
Table 1 for description of institutions.
outcomes that students are expected to achieve. At the same
time, the conceptual framework provides students with scaffolding for their learning about the mechanisms that underlie
whatever phenomenon they are attempting to master. The
scaffolding provided by core concepts extends across all of
physiology (they are generalizable and transferable) and can
aid students in a course and can continue to serve this function
as they progress through subsequent physiology courses.
We have noted that the conceptual framework for cell-cell
communication is large, made up of 51 items, and complex,
with up to 4 levels in the hierarchy. It is likely that many
instructors in undergraduate courses do not expect students to
know (understand) all of the 51 items contained in the cell-cell
communications conceptual framework, although students in
more advanced courses might well be expected to do so.
There are several ways in which the cell-cell communication
conceptual framework can be reduced in size and/or complexity to meet the needs of an introductory physiology course. In
our development of the homeostasis conceptual framework (5),
we eliminated all items that received fewer than 30% Essential
ratings from our faculty cohort. The 21 items in the conceptual
framework in Table 1 with an asterisk would be eliminated
using this rule. Another approach would be to eliminate all four
of the items at the fourth (deepest) level in our hierarchy. Our
results show that these items are rated as less important than
items higher in the hierarchy.
However, the problem with applying such algorithmic approaches to editing the conceptual framework is that the
remaining items may not adequately describe the features of
the physiological mechanisms that instructors want their students to master. For example, the 30% rule described above
(see Table 2) would result in elimination of 10 items at the
second level, 7 items at the third level, and 4 items at the fourth
level. This procedure seems to us to remove items that may
well be important for students in at least some introductory
courses.
The problem of editing the cell-cell communication conceptual framework is ultimately only solvable by each individual
instructor creating a conceptual framework that is appropriate
for the students in his or her particular course. Our version of
the conceptual framework (Table 2) is not the only possible
way to unpack the core concept of cell-cell communication.
The conceptual framework we have described here is NOT a
prescription for what is important for learning physiology; it is
a guide to understanding this core concept.
One final issue should be noted. Physiology textbooks may
identify “cell-cell communication” as a general model for
thinking about the endocrine system (see, for example, Ref.
15), but it is rare for this core concept to be extended to the
nervous system and the electrical coupling of cells. Thus
instructors will need to be vigilant in using the terminology of
cell-cell communication wherever it is appropriate to so. In this
way, the students can be reminded that this core concept
applies in a great many systems.
We will be seeking additional validation of the cell-cell
communication conceptual framework through interactions
with faculty at local and national biology and physiology
meetings. The next step will be the writing of a concept
inventory for the core concept of cell-cell communication.
VALIDATED CONCEPTUAL FRAMEWORK FOR COMMUNICATIONS
ACKNOWLEDGMENTS
We acknowledge the contributions to this work made by all of our
colleagues who participated in our survey and those who interacted with us in
other ways as the cell-cell communication conceptual framework was being
developed and validated. We especially acknowledge the many contributions
that Ann Wright made to the work described in this paper.
GRANTS
This work was supported in part by a grant from the National Science
Foundation to J. McFarland (Due-1043443) and, in part, by a grant from the
Czech Science Foundation to P. Martinkova (GJ15–15856Y).
DISCLAIMERS
Any results, conclusions, or recommendations expressed in this paper are
those of the authors and do not necessary reflect the views of the two funding
agencies.
No conflicts of interest, financial or otherwise, are declared by the author(s).
AUTHOR CONTRIBUTIONS
J. Michael, J. McFarland, A.W., W.C., H.I.M., and M.P.W. conceived and
designed research; J. Michael and J. McFarland performed experiments; J.
Michael and P.M. analyzed data; J. Michael, P.M., J. McFarland, A.W.,
W.C., H.I.M., and M.P.W. interpreted results of experiments; J. Michael
and P.M. prepared figures; J. Michael drafted manuscript; J. Michael, P.M.,
J. McFarland, A.W., W.C., and H.I.M. edited and revised manuscript; J.
Michael approved final version of manuscript.
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