The Sensitive, Muscular Cell
This is a preliminary draft of one chapter of a book-in-progress
tentatively entitled, “Evolution As It Was Meant To Be — And the Living Narratives That Tell Its Story”.
You will find
a fairly lengthy article serving as a kind of extended abstract of major
parts of the book. This material is part of the
Biology Worthy of Life
Project. Copyright 2017-2021
The Nature Institute.
All rights reserved. Original publication: May 7, 2019.
Last revision: May 7, 2019.
Throughout a good part of the twentieth century, cell biologists battled
over the question, “Which exerts greater control over the life of the cell
— the cell nucleus or the cytoplasm?”
From mid-century onward, however, the badge of imperial authority was, by
enthusiastic consensus, awarded to the nucleus, and especially to the
genes and DNA within it. “Genes make proteins, and proteins make us” —
this has been the governing motto, despite both halves of the statement
being false (which will become ever clearer as we proceed).
The question for our own day is, “Why would anyone think — as the majority
of biologists still do — that any part of a cell must possess executive
control over all the other parts?” We have already caught our
first glimpse of the performances in the nucleus (see
and these hardly testify to domination by a single, controlling agent.
Now we will broaden our outlook by making a first approach to the rest of
the cell — the cytoplasm, along with its organelles and enclosing
It would be well to remind ourselves before we proceed, however, that,
whatever else it may be, an organism is a physical being. Its doings are
always in one way or another physical doings. This may seem a
strange point to need emphasizing at a time when science is wedded to
materialism. And yet, for the better part of the past century problems
relating to the material coordination of biological activity were largely
ignored while biologists stared, transfixed, into the cell nucleus. If
they concentrated hard enough, they could begin to hear the siren call of
a de-materialized, one-dimensional, informational view of life.
The idea of a genetic code and program proved compelling,
even though the program was never found and the supposedly fixed code was
continually rewritten by the cell in every phase of its activity. So long
as one lay under the spell woven by notions of causally effective
information and code, problems of material causation somehow disappeared
from view, or seemed unimportant. And so, freed from “mere” material
constraint, programmatic Information became rather like the Designer of
the intelligent design advocates.
Surely, even if they are not the decisive causes usually imagined, genes
do connect in some manner with the features they were thought
one-sidedly to explain. But this just as surely means they must connect
physically and meaningfully, via movements and transformations of
substance testifying to an underlying narrative
— not merely logically, through the genetic encoding of an imagined
program. And what we saw in
about the significant movements and gesturings of chromosomes is only the
beginning of the story.
Does the cell possess its
own “senses” and “limbs”?
Let’s continue by taking note of the cytoskeleton
which plays a key role in the cell’s physical movement. It consists of
many exceedingly thin molecular filaments and tubules, visible only under
powerful microscopes. Many of these are growing at one end and perhaps
shrinking at the other end, or else disassembling altogether even as new
filaments are establishing themselves. Through this dynamic activity —
this constant growth and dissolution of minuscule fibers — the cell gains
its more or less stable shape and organization. Cellular organelles, to
which the cytoskeleton attaches, are positioned and re-positioned as the
cytoskeleton somehow “senses” internal needs, while also responding to
external stresses such as stretching or compression. Beyond that, the
filaments and tubules, by dynamically managing the distribution of forces
within the cell as a whole, help to enable and guide its movements so that
it can find its proper place among the millions of cells in its immediate
A cultured fibroblast cell, specially prepared so as to show features of the
cytoskeleton in artificial color: narrow actin filaments (blue); wider
and intermediate filaments (red). The dark and roughly circular
(spherical) region near the center is the cell
And the cells of our bodies do move. Literal rivers of cells shape the
young embryo. So, too, migrating cells in and around a wound cooperate in
restoring the damaged architecture. In every tiniest hair follicle niche,
as well as throughout our tissues generally, cells move, replace dying
neighbors, and reorganize themselves. And even while remaining in one
place, cells must continually adapt their form to their immediate
environment — certainly a major task in the rapidly growing embryo and
fetus. But the stresses and tensions of that environment are in turn the
partial result of interconnected cytoskeletal activities in all the cells
of the local tissue.
The cytoskeleton not only supports cell migration, but also provides
pathways for the orchestrated movement of substances within the cell. A
protein molecule is not of much use if it cannot find its way to where it
is required. Individual molecules and protein complexes are shifted about
along these cytoskeletal pathways, as are the voluminous contents of
large-capacity, membrane-bound, transport structures (“vesicles”). These
latter can “bud off” from various membranes of the cell and then move,
along with their cytoplasmic contents, to a particular destination where,
having released their contents, they are degraded and recycled.
Such directed movements are essential to the life of the cell. Where an
enzyme or signaling molecule goes in a cell is decisive for its function.
Some molecules, for example, are outward-bound to, and through, the cell
surface on signaling missions to distant reaches of the body. Meanwhile,
others are inward-bound on different signaling missions. (Hormones,
secreted by cells of a gland at the start of their journey, and then
received by cells in various other parts of the body, illustrate both
sorts of movement.) Some molecules produced in a cell are destined for a
particular locus on the highly differentiated cell membrane, while others
are targeted to any of a virtually infinite number of possible stopping
places somewhere in the cell’s “intricate landscape of tubes, sacs,
clumps, strands and capsules that may be involved in everything from
intercellular communication to metabolic
But the cytoskeleton is not just a cytoskeleton. The filaments and
tubules themselves are teeming with associated regulatory molecules. As
of a decade ago more than 150 proteins capable of binding to just one type
of filament — actin — had already been identified. As one researcher has
put it: “Despite the connotations of the word ‘skeleton’, the cytoskeleton
is not a fixed structure whose function can be understood in isolation.
Rather, it is a dynamic and adaptive structure whose component polymers
and regulatory proteins are in constant flux”
There is scarcely any aspect of cellular functioning in which the
cytoskeleton fails to play a role. On the exterior side, it connects with
the cell’s outer (“plasma”) membrane, where it helps to import substances
from the environment while also facilitating the adhesion of extracellular
molecules and other cells. Through its interaction with the extracellular
matrix, it contributes to the mechanical stiffness and coherence of entire
tissues. On the interior side, it engages with the nuclear membrane and
the specialized filaments underlying that membrane. These filaments are
vital regulators of gene expression. In this way the cytoskeleton links
various sorts of extracellular signals, both mechanical and biochemical,
to the nucleus and its chromosomes, providing a foundation for holistic
behavior involving much more than the individual cell.
There are many ways to affect gene expression, and they do not all occur
in the cell nucleus. For example, a key part of this expression is the
translation of RNA molecules into proteins, which occurs in the cytoplasm.
Evidence suggests that “the physical link between cytoskeletal and
translational components helps dictate both global and local protein
synthesis”. But (as is all too typical) the causal effects work both
ways: “specific translation factors are able to affect the organization of
The cytoskeleton plays many other roles, not least by ensuring the proper
separation of mitotic chromosomes, the division of a cell into two
daughter cells, and the correct allocation of chromosomes to those
daughter cells. (See
where the mitotic spindle, shown in green, consists of cytoskeletal
fibers.) It is perhaps unsurprising, then, that some have seen the
cytoskeleton, with its nuanced organizational “skills”, as the seat of
cellular intelligence or the “brain” of the cell. However, we need not
invite a misleading anthropomorphism in order to acknowledge the subtle
and nuanced organizational activity — the narratively intelligible
— realized through the dynamics of cytoskeletal movement.
One thing is certain: neither the cytoskeleton’s moment-by-moment dynamics
nor the coherent and intelligible aspect of its activity can be ascribed
to “instructions” from genes — or even to the physical laws bearing on
cytoskeletal proteins. As the matter was summarized by Franklin Harold,
an emeritus professor of biochemistry and molecular biology at Colorado
State University, “One cannot predict the form or function of these
complex [cytoskeletal] ensembles from the characteristics of their
component proteins”. And yet, Harold went on, “When seen in the context
of the parent cell the arrangement of the molecules becomes quite
comprehensible.” He then raised the obvious question: “How is the
cytoskeleton itself so fashioned that its operations accord with the
cell’s overall ‘plan’ and generate its particular morphology time after
(Harold 2001, p. 125).
Harold answered the question merely by expressing confidence that
understanding will eventually come. And surely it will. But we can be
equally sure that it will not come before we have penetrated more deeply
the problem: How does a living context, or whole — in this case, the cell
with its “overall plan” — manage to express itself through all its parts?
In an integral, organic whole, we can assume the “viewpoint” of many parts
in such a way as to make each one momentarily seem to be the
coordinating “master” element. This is why the cytoskeleton, just as much
as our genes, might appear to explain everything that goes on. With
wonderful sensitivity it “feels out” the surfaces of the cell and all its
organelles. The balance of forces maintained by the fibers shapes the
cell, dynamically positions the organelles, and both guides and helps to
power the critical movement of the cell within its environment. As we
have seen, the cytoskeleton likewise plays a key role in moving substances
to their functional locations within the cell. And it is a decisively
important regulator of gene activity.
And yet, this does not make the cytoskeleton a master regulator. The
truth is simply that, to one degree or another, each part of an organic
whole bears that whole within itself — is informed by, and expresses, the
whole. The idea of a master regulator arises only when we insist on
viewing a specific part in isolation from the whole so as to identify
single, local, and unambiguous causal interactions. We then say that this
part makes certain things happen. The fact that the part is itself
made to happen by the very things it supposedly accounts for then tends to
be ignored. We lose sight of the fluidity and physical indeterminism of
the living context — an indeterminism whose meaning and coherence become
visible only when we allow particular physical causes to “disappear” into
the unifying narratives, or stories, of the organism’s life
In much the same way, we experience physical sounds and gestures
disappearing into the meaning of our speech.
The sensitive “skin” and
organelles of the cell
Interestingly, the cell membrane (“plasma membrane”) is likewise a highly
dynamic feature that has been seen as a decisive coordinator of cellular
activity, and even as a seat of cellular intelligence. It is here that we
see “decisions” continually being made about which substances and signals
— from among the endlessly streaming crowds passing through the
neighborhood — are to be admitted into the cell and which ones are
“foreign”, or else unnecessary at the moment. Here, perhaps more than
anywhere else, is where cellular identity is established and “self” is
distinguished from “other”. This happens partly by means of protein
receptors (“sensors”) embedded in, or attached to, the lipid matrix of the
Here, too, everything flows (which is one reason why any image like the
two below is a kind of frozen lie, despite being useful when approached
with the right awareness). Molecules continually associate with, and
dissociate from, the membrane, even as they undergo various modifications
that redirect their functioning. They also migrate within the membrane,
forming specialized communities that are in no two locales exactly the
same. All the while portions of the membrane, along with cytoplasmic
contents, are “pinched off” as more or less spherical vesicles that, once
they are fully detached, move elsewhere, either externally to the cell or
internally. At the same time, selected vesicles from external sources
fuse with the membrane and release their contents into the cell’s
Schematic representation of a cell membrane: a lipid bilayer (red spheres
with yellow tails) along with embedded proteins and other molecules. Many
of the embedded proteins, which are dynamically distributed, function
as “sensors” or receivers of molecular
Schematic representation of the internal membrane systems of a nucleated
Much the same is true of all the interior membranes delimiting the various
organelles of the cell (Figure 4.3.) These, too, “harbor sensitive
surveillance systems to establish, sense, and maintain characteristic
physicochemical properties that ultimately define organelle identity.
They … play active roles in cellular signaling, protein sorting,
and the formation of vesicular
Membranes, then, not only structure the cell into distinctive compartments
and organelles, but they also “oversee” the characteristic and essential
contents of those compartments and play decisive roles in managing the
ceaseless and massive intercommunication among them.
All this finely discriminating activity is going on, as the eminent cell
biologist, Paul Weiss, wrote in 1973, while “the cell interior is heaving
and churning all the time”
(Weiss 1973, p. 40).
Everything is watery movement of substances and transformation of
organizational structure, and yet the cell’s identity and unified
character are maintained. Movement itself is what expresses the character
and life of the cell and the organism. The intricately choreographed
flows and chemical transactions in plasm and membrane are responsive to
the ever-unpredictable conditions of the moment, and are the means by
which the cell not only stays true to itself, but also remains in harmony
with its larger environment.
The dynamics of this material accomplishment are a long way from the
clean, informational logic commonly associated with genes. Lenny Moss, a
molecular biologist who transformed himself into one of our most
insightful philosophers of biology, had this to say about the relation
between cellular membranes and genes:
The membranous system of the cell, the backbone of cellular
compartmentalization, is the necessary presupposition of its own renewal
and replication. Cellular organization in general and membrane-mediated
compartmentalization in particular are constitutive of the biological
"meaning" of any newly synthesized protein (and thus gene), which is
either properly targeted within the context of cellular
compartmentalization or quickly condemned to rapid destruction (or
cellular "mischief"). At the level of the empirical materiality of real
cells, genes "show up" as indeterminate resources ... If cellular
organization is ever lost, neither "all the king’s horses and all the
king’s men" nor any amount of DNA could put it back together
From information to life
Returning for a moment to our introductory question about the control of
the cell by its genes: perhaps we have now gained our first feeling for
how the cell and organism as a whole can flexibly and contextually express
itself through any one of its parts, including its DNA and chromosomes — a
fact we will get much more specific about in the Technical Supplement, as
well as in
If we think of the genome as an almost infinitely complex informational
structure, there is no reason not to think, for example, of the
cytoskeleton and membranes of a cell as at least equal bearers of vital
information. However, it also important to recognize the illegitimate
aspects of this comparison.
In particular, the concept of information as normally applied to DNA is a
quantitative one. It depends on the existence of discrete, iterated
elements (“letters” of the “code”), any one of which can take on certain
precise values. But everything we know about the “heaving and churning”
interior of the cell — including even the coiling and looping of
chromosomes we saw in
— tells us that we are looking at boundless and continuous variations of
form and gesture whose depth of meaning is both non-quantifiable and
vastly more profound than any quantifiable features we can abstract from
To ask about the amount of information in various aspects of the cellular
performance (including the performance of chromosomes) is rather like
asking about the amount of information in Stravinsky’s ballet, “The Rite
of Spring”. It would be one thing to define informational quantities in
terms of some more or less arbitrary method of choreographic notation
(“code”), and quite another to consider the expressive content of the
So, too, our means for quantifying the informational content of a genomic
sequence bears little relation to the material gestures expressing the
cell’s life. The truth here will become even more vivid when we look (in
at the context-dependence that biologists freely acknowledge at every
Figure 4.1 credit: Courtesy of Harald Herrmann, University of
Here is a further description (from
Plankar et al. 2012)
of the various roles of the cytoskeleton:
The cytoskeleton, in addition to its classical structural-mechanical role,
integrates many signalling pathways, influences the gene expression,
coordinates membrane receptors and ionic flows, and localizes many
cytosolic enzymes and signalling molecules, while at the same time it
represents an immense, electrically active catalytic surface for metabolic
interactions. Together with cell adhesion molecules and the extracellular
matrix, it forms a tensionally integrated system throughout the tissues
and organs, which is able to coordinate gene expression via
mechano-transduction. Given the strong relationship between mechanical and
electromagnetic excitations in the microtubules (piezoelectricity) and
their well-established organising potential, a weakened EM field may
thus influence both cell and tissue aspects of carcinogenesis.
Kim and Coulombe 2010.
The use of words such as “dictate” to suggest unambiguous causation is
extremely common in all the literature of molecular biology. And almost
as common is the immediate contradiction of this language, as we see here.
For more on this, see
Figure 4.2 credit: Mariana Ruiz, edited by Alokprasad84.
Figure 4.3 credit: Mariana Ruiz Villareal.
Radanović, Reinhard, Ballweg et al. 2018.
Moss 2003, p. 95.
Pages 76-98 in Moss’ book provide an excellent overview of the dynamics
associated with cellular membranes.
Fletcher, Daniel A. and R. Dyche Mullins (2010). “Cell Mechanics and the
Cytoskeleton”, Nature vol. 463 (Jan. 28), pp. 485-92.
Harold, Franklin M. (2001). The Way of the Cell: Molecules, Organisms
and the Order of Life. Oxford: Oxford University Press.
Kim, Seyun and Pierre A. Coulombe (2010). “Emerging Role for the
Cytoskeleton as an Organizer and Regulator of Translation”, Nature
Reviews Molecular Cell Biology vol. 11 (Jan.), pp. 75-81.
Kwok, Roberta (2011). “The New Cell Anatomy”, Nature vol. 480
(Dec. 1), pp. 26-8.
Moss, Lenny (2003). What Genes Can’t Do. Cambridge MA: MIT Press.
Plankar, M., Del Giudice, E., Tedeschi, A., and Jerman, I. (2012). “The
Role of Coherence in a Systems View of Cancer Development”, Theoretical
Biology Forum vol. 105, no. 2 (Jan. 1), pp. 15-46.
Radanović, Toni, John Reinhard, Stephanie Ballweg et al. (2018). “An
Emerging Group of Membrane Property Sensors Controls the Physical State of
Organellar Membranes to Maintain Their Identity”, Bioessays.
Sapp, Jan (1987). Beyond the Gene: Cytoplasmic Inheritance and the
Struggle for Authority in Genetics. Oxford: Oxford University Press.
Weiss, Paul (1973). The Science of Life: The Living System — A System
for Living. Mount Kisco NY: Futura Publishing.
Steve Talbott :: The Sensitive, Muscular Cell