The universal dynamics of cell spreading

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Original entry: Naveen Sinha, APPHY 226, Spring 2009

In numerous biological experiments, cells are plated onto an artificial adhesive surface to study them under a microscope. After being deposited on the surface, they flatten and spread outwards along the surface. This process incorporates many biological reactions, including the diffusion of adhesion receptors and the polymerization of the scaffolding-like actin molecules. However, Prof. Mahadevan and his collaborators show how a variety of cells and surface exhibit a power-law behavior in the contact radius of the colony of cells as a function of time. This can be understood when the cells are modeled as a viscous shell of liquid with a much less viscous interior.

The basic biological system is shown below. Cells are placed on a surface and Reflectance Contrast Imaging Microscopy is used to measure the contact area as a function of time.


The length measure used to characterize the system is the radius of a circle with the same area. On a log-log plot, the power law behavior becomes apparent.


There appear to be two different regimes: (1) an initial diffusive regime with <math>R ~ t^{1/2}</math> and (2) a sub-diffusive region with <math>R ~ t^{1/4}</math>.

Despite all the biochemical complexities of the spreading process, a simple model that treated the cells as a shell of viscous liquid is sufficient to describe most of the behavior.


Initially, the power-law can be derived by setting the chance in adhesion energy equal to the viscous energy dissipation. This approximation is valid for when the radius of the contact angle is less than te initial cell radius <math>R_c</math>. The change in contact area is related to the rate of change in the radius by <math>\frac{dA}{dt} = R \frac{dR}{dt}</math>. This can related to the rate of energy gain by multiplying by the adhesion energy per unit area, J, which is the product of the area of each bond and the energy per bond: <math>J R \frac{dR}{dt}</math>. Assuming that the cell cortex has a width w everywhere, the strain is of the order <math>\frac{dR/dt}{w}</math>. This strain acts over a volume approximately equal to <math>R^2 w</math>. The product of the strain, volume, and viscosity leads to an energy dissipation of <math>\eta (\frac{dR}{dt} \frac{1}{w})</math>. By setting this equal to the change in the adhesion energy, we can get the following power law: <math>R = C \big(\frac{J w}{\eta}\big)^{1/2} t^{1/2}</math>.

At longer times, when cell has flattened out (i.e. the radius of contact is larger than the initial radius), the viscous energy dissipation occurs throughout the whole volume of the cell. The power law is modified to <math>J R \frac{dR}{dt} = \eta_c \big(\frac{dR}{dt} \frac{1}{w}\big)^2 R^2 w_c</math>. This can be re-arranged to the scaling law: <math>R ~ \big(\frac{J R_c^3}{\eta_c}\big)^{1/4} t^{1/4}</math>.

One prediction of this model is that the properties of the cellular membrane are far more important than the interior of the cell in the cell spreading. One way to test this is by creating two mutants: one in which the microtubules molecules within the cell are unable to polymerize and another in which the actin shell in the cortex is altered.


Sung Hoon's comment: In the Fig. 4 (a), the Cytochalasin D-treated cell showed linear
behavior. What does the treatment do so that the treated cells spread more quickly?
Has anyone actually created these mutant cells to test this theory? Is that what you're showing below?
Maybe it's better to write your own captions that get right to your point?
--Lidiya 03:06, 18 February 2009 (UTC)

This work is important by providing unity to the plethora of information about the molecular mechanics for cell motility and adhesion. It allows future researchers to focus on the aspects of cell structure that are most relevant for thee processes and make refinements to this basic model.

Second Entry: Nick Chisholm, AP 225, Fall 2009 (In Progress...)

General Information

Authors: D. Cuvelier, M. Thery, Y-S. Chu, S. Dufour, J-P. Thiery, M. Bornens, P. Nassoy, and L. Mahadevan

Publication: Current Biology 17 694 (2007)

Soft Matter Keywords

Adhesion, Cell, Polymerization, Viscous


The authors explore the early stages of cell spreading. In particular, they look at the situation where cells are plated onto artificial adhesive surfaces; they first flatten and deform extensively as they spread. This article presents experimental probing of the dynamics of this spreading process using quantitative visualization and biochemical manipulation with a variety of cell types, adhesive surfaces, adhesion receptors, and cytoskeleton-altering drugs. Surprisingly, the authors find that the adhesion dynamics of cells follow a universal power-law behavior (i.e. the contact radius is proportional to elapsed time to a certain power).

In Figure 1, one can see an image of a cell spreading on a substrate. The image is taken using reflection interference contrast microscopy (RICM).

Figure 1, taken from [1].

Soft Matter Discussion

As is clear by Figure 1, the spreading is isotropic, the authors can define the spreading radius as: <math>R = \sqrt{\frac{A}{\pi}}</math>.

The contact radius was found as a function of time for various cells, adhesive surfaces, adhesion receptors, and cytoskeleton-altering drugs; the results are plotted in Figure 2 (careful: it's a logarithmic plot!). From this plot, the authors notw to regimes: an initial diffusive regime summarized by the scaling law <math>R \proportional t^{1/2}</math>

Figure 2, taken from [1].


[1] D. Cuvelier, M. Thery, Y-S. Chu, S. Dufour, J-P. Thiery, M. Bornens, P. Nassoy, and L. Mahadevan, "The universal dynamics of cell spreading," Current Biology 17 694 (2007).