“Stochastic Resonance” for Individual Cells

Main Text

Particles fluctuating in a double well have enjoyed a long-standing interest in physics, both in experiments and in theory (1,2). If hopping is possible between two wells, how will the statistics be affected by the shapes of the potentials and by noise? This question, apparently far from biological significance, now finds new relevance in the context of cell motility, where “noise” is internally driven by activity of the actomyosin cytoskeleton.

In this issue of the Biophysical Journal, Fink et al. (3) report an assay in which single cells hop between two adhesive motifs connected by a thin bridge over days (Fig. 1 a). They adhere on surfaces microcontact printed with a protein of the extracellular matrix, fibronectin. The cells fluctuate in shapes by growing protrusions through actin polymerization, and if they reach the neighboring motif, they adhere through focal contacts and eventually move there. The authors show that distributions of dwelling times in both motifs are symmetric if adhesive motifs have the same symmetry and the same area. They become asymmetric if cells become preferentially polarized following an asymmetric shape imposed by one of the adhesive patterns.

Figure 1.

A cell in an asymmetric double-well potential. (a) A two-state micropatterned assay with an asymmetric shape. A cell hop between motifs with higher dwelling times on anisotropic regions (in this case the triangle) (adapted from (3)). Scale bars, 25 μm. (b) A cell as a fluctuating particle in an asymmetric potential. The cell is seen as a particle migrating in a potential W with two different wells W(x₁) and W(x₂) representing the two different patterns. To see this figure in color, go online.

This report shows that distributions of cells mimic behaviors of fluctuating particles in a double-well potential (Fig. 1 b). However, this experiment also demonstrates that the activity of cells can lead to new features when compared to passive colloids: cell polarization and its memory seem to play a key role. A potential next step based on these experiments could be to bridge the gap between active gel theory, which encodes cell polarization in a mesoscopic parameter (4), and actual measures extracted from these motility assays.

This article shows that biological physics can now tackle questions in the same way physics of liquid crystal successfully solved questions: boundary conditions at surfaces are controlled (5,6), measures are sufficiently quantitative to extract numbers, and theory gives predictions that can be tested experimentally. This simple setup, and more broadly, motility assays with controlled anchorage conditions (7, 8, 9), could reveal new ways of understanding the physics of cell motion in a quantitative manner, as in other fields of physics. The outcome should also open novel avenues in out-of-equilibrium physics with insight into biology.

Editor: Kinneret Keren.