Unveiling the Hidden Language of Extracellular Matrix Deformations: A tale of cellular whispers and unstable fibers

One of the key questions in cellular biology revolves around comprehending the intricate interplay between an individual cell and its neighboring counterparts within a tissue. Beyond the cell’s innate genetic blueprint, external influences, such as those exerted by its microenvironment, drive most of its functions. The main component of this microenvironment is the Extracellular Matrix (ECM), a convoluted network of fibrous proteins which interact directly with cells. The ECM serves as a scaffold that facilitates intercellular signal exchange, including biomechanical forces. Cells actively respond to mechanical action and induce deformation patterns which take the form of bands that interconnect neighbouring cells. These bands include tracts of elevated matrix densification and fiber alignment and orchestrate vital cellular processes like migration, invasion and proliferation, while there is strong evidence of their contribution to intercellular communication. Unraveling the mechanisms underpinning these phenomena equates to deciphering the mechanical properties of ECM and by that, the mechanical traits of its constituent fibers. Prior research into the mechanics of fibers has uncovered unusual mechanical phenomena driven in part by their inherent hierarchical structure. These phenomena encompass unique behaviors such as unstable responses of fibers when subjected to compressive loads. This instability is characterized by transitions from heightened fiber stiffness (in which the fiber becomes harder) to the loss of fiber stiffness (causing the fiber to become less stiff and buckle).
In light of these findings, we have developed models that encompass the distinct intrinsic characteristics of fiber structure and mechanics, and investigate deformations of the Extracellular Matrix (ECM) induced by cells. We have analyzed and modelled the mechanical properties of the ECM from a macroscopic perspective. Our fundamental assumption is that individual fibers can withstand tension but buckle and collapse when subjected to compression. We compare two families of fiber mechanics models: Family 1, characterized by stable responses of individual fibers under compression, and Family 2, exhibiting unstable responses of individual fibers under compression. Our simulations expose diverse compression instabilities inherent to each Family. These instabilities lead to the formation of densely packed ECM regions, featuring strongly aligned fibers. These regions emanate either from individual contractile cells or join neighboring cells, mirroring observations from experiments. We show that both fiber alignment and ECM densification are prevented in the absence of elevated compression. Our models demonstrate that material instabilities wield a dominant role in the mechanical behavior of the fibrous ECM. Despite substantial disparities in the responses of the two model families, our research underscores the pivotal role played by compression instabilities in the behavior of fibrous biological tissues. This has implications to a number of cellular and tissue processes, particularly in understanding cancer invasion and metastasis. Our findings introduce novel perspectives for investigating how fibers respond to deformations induced by cells and the ensuing implications for biomechanical interactions between cells.