Studying the relationship between the size and the anatomy and physiology of living organisms has proven useful in deciphering what the key physical constraints are that apply to them. For instance, total adhesive pad area is found to scale like organism mass over a wide variety of animal species, possibly to resist against body weight.

In this study, we apply this approach at the cell scale to ask how large-scale geometrical constraints affect the organization of adhesion patches and the size of cell-substrate contact at different stages of the cell spreading process. Indeed, cells, like many animals, adhere to their substrate. For that, they use specific protein complexes, called focal adhesions, which form patches often situated at the cell periphery.

The image on the cover of the August 19 issue of Biophysical Journal shows the organization of paxillin, a major component of focal adhesions, imaged by total internal reflection fluorescence microscopy at the final stage of spreading, in the three different geometries that have been tested for this article. At the center, the pattern observed corresponds to a fibroblast (the cell type used in this study) spreading on a single glass plate; on top, to a fibroblast of larger volume spreading in the same geometry; and, at the bottom, to a fibroblast confined between two parallel glass plates.

Cells analyzed in this study presented the archetypal shape of a cell spreading on a substrate, with a central cell body that while flattening, retains a spherical cap shape, and is surrounded by a flat actin-rich compartment called the “lamella.” We show that this shape is preserved isometrically regardless of cell volume and confinement variations. In addition, as can be guessed from the cover images, the adhesion patches collectively follow an isometric scaling with respect to cell spread area. We demonstrate that this isometry follows from the restriction of the distribution of focal adhesions to the lamella, whose length scales like cell radius.

Adhesion distribution is crucially important for various cell functions. For instance, cells spread and adhere after mitosis but detach partially from their substrate to initiate migration. The allometries that we reveal here demonstrate that cell-scale mechanisms can regulate the organization of adhesion patches. They also represent an interesting example of how global geometrical constraints can influence the local organization of molecular actors to control a cellular process.

To learn more about our research, visit: https://jonfouchard.github.io/perso.github.io/collaborations.

 — Célian Bimbard, Ali-Alhadi Wahhod, Démosthéne Mitrossilis, Joseph Vermeil, Rémi Bousquet, Alain Richert, David Pereira, Pauline Durand-Smet, Sophie Asnacios, Jocelyn Étienne, Atef Asnacios, and Jonathan Fouchard