Does cell biology need physicists?

The American Physical Society has an online journal, Physics, with the goal of making recent research accessible to a wide audience. The journal website states:

Physics highlights exceptional papers from the Physical Review journals. To accomplish this, Physics features expert commentaries written by active researchers who are asked to explain the results to physicists in other subfields. These commissioned articles are edited for clarity and readability across fields and are accompanied by explanatory illustrations.

One recent paper that caught my eye was an essay written by Charles Wolgemuth, titled “Does Cell Biology Need Physicists?” Wolgemuth asks key questions in the introduction to his essay.

The past has shown that cell biologists are extremely capable of making great progress without much need for physicists (other than needing physicists and engineers to develop many of the technologies that they use). Do the new data and new technological capabilities require a physicist’s viewpoint to analyze the mechanisms of the cell? Is physics of use to cell biology?

Later in the essay, Wolgemuth asks his central question in a more specific way:

It is possible that the physics that cells must deal with is slave to the reactions; i.e., the protein levels and kinetics of the biochemical reactions determine the behavior of the system, and any physical processes that a cell must accomplish are purely consequences of the biochemistry. Or, could it be that cellular biology cannot be fully understood without physics?

Readers of the 4th edition of Intermediate Physics for Medicine and Biology are likely to scream “Yes!” to these questions. I too enthusiastically answer yes, but I agree with Wolgemuth that it is proper to ask such basic questions occasionally.

I should add that Russ Hobbie and I tend to look primarily at macroscopic phenomena in Intermediate Physics for Medicine and Biology, such as the biomechanics of walking with a cane, the interpretation of an electrocardiogram, or the algorithm required to form an image of the brain using a CAT scan. We occasionally look at events on the atomic scale, but for the most part we ignore molecular biophysics. Yet, the cellular scale is an interesting intermediate level that is becoming a fertile field for the applications of physics to biology. Indeed, I examined this issue when discussing the textbook Physical Biology of the Cell last year in this blog. The discussion that Russ and I give to fluid dynamics, diffusion, and bioelectricity in Intermediate Physics for Medicine and Biology is relevant to cellular topics.

To answer his question, Wolgemuth provides five examples in which physics provides key insights into cellular biology: 1) Molecular motors, 2) Cellular movement, 3) How cells swim, 4) Cell growth and division, and 5) How cells interact with the environment. One of my favorite parts of the essay is the consideration of potential pitfalls for physicists in biology.

Fifteen years ago, around the time that I began working in biophysics, there were very few collaborations between physicists and cell biologists, especially if the physicists were theorists. Theory was, and still is to a good degree, a word that should be avoided in the presence of biologists. Those of us who use math and computers to try to understand how cells work tend to call ourselves modelers instead of theorists. My suspicion is that many of the first physicists and mathematicians who tried to develop models for how biology works attempted to be too abstract or too general. As physicists we like to try to find universal laws, and though there are undoubtedly general principles at play in cell biology, it is likely that there are no real universal rules. Evolution need not find only one way to do something but more often probably finds many. Rather than search out generalities, we will serve biology better if we deal with specifics. As Aharon Katchalsky, who is largely credited with bringing nonequilibrium thermodynamics to biology, purportedly said, “It is easier to make a theory of everything than a theory of something.”

In recent years, physicists have done a much better job at addressing specific problems in biology. However, there still remains a divide between the two communities. Indeed, good physical biology that comes out of the physics community often goes unnoticed or is under appreciated. The burden falls on us to properly convey our work so as to be accessible to biologists. We need to make conscious efforts at communication and dissemination of our results. Two useful approaches toward this end are to publish in broader audience journals that reach both communities, and for papers that contain theoretical analyses to provide a qualitative description of the modeling in the main text, while leaving the more mathematical details for the appendices or supplemental material (for further discussion of this topic, see Ref. [55]). It is also of prime importance to maintain and to forge new connections between physicists and biologists.

Wolgemuth comes closest to answering his own questions near the end of the essay, where he predicts

To be truly successful, we must provide an understanding of biology that spans the gorge from biochemistry and genetics to cellular function, and do it in such a way that our models and experiments are not only informative about physics, but directly impact biology.

Cell biology is awaiting these descriptions. And it may be that physicists are the most able to draw these connections between the protein level description of cellular biology that currently dominates and a more intuitive, yet still quantitative, description of the behavior of cells and their responses to their environments.