Mechanisms and in vivo functions of contact inhibition of locomotion

Contact inhibition of locomotion (CIL) is a process whereby a cell ceases motility or changes its trajectory upon collision with another cell. CIL was initially characterized more than half a century ago and became a widely studied model system to understand how cells migrate and dynamically interact. Although CIL fell from interest for several decades, the scientific community has recently rediscovered this process. We are now beginning to understand the precise steps of this complex behaviour and to elucidate its regulatory components, including receptors, polarity proteins and cytoskeletal elements. Furthermore, this process is no longer just in vitro phenomenology; we now know from several different in vivo models that CIL is essential for embryogenesis and in governing behaviours such as cell dispersion, boundary formation and collective cell migration. In addition, changes in CIL responses have been associated with other physiological processes, such as cancer cell dissemination during metastasis

Connecting individual to collective cell migration

Abstract Collective cell migration plays a pivotal role in the formation of organs, tissue regeneration, wound healing and many disease processes, including cancer. Despite the considerable existing knowledge on the molecular control of cell movements, it is unclear how the different observed modes of collective migration, especially for small groups of cells, emerge from the known behaviors of individual cells. Here we derive a physical description of collective cellular movements from first principles, while accounting for known phenomenological cell behaviors, such as contact inhibition of locomotion and force-induced cell repolarization. We show that this theoretical description successfully describes the motion of groups of cells of arbitrary numbers, connecting single cell behaviors and parameters (e.g., adhesion and traction forces) to the collective migration of small groups of cells and the expansion of large cell colonies. Specifically, using a common framework, we explain how cells characterized by contact inhibition of locomotion can display coherent collective behavior when in groups, even in the absence of biochemical signaling. We find an optimal group size leading to maximal group persistence and show that cell proliferation prevents the buildup of intercellular forces within cell colonies, enabling their expansion

The front and rear of collective cell migration

International audienceCollective cell migration has a key role during morphogenesis and during wound healing and tissue renewal in the adult, and it is involved in cancer spreading. In addition to displaying a coordinated migratory behaviour, collectively migrating cells move more efficiently than if they migrated separately, which indicates that a cellular interplay occurs during collective cell migration. In recent years, evidence has accumulated confirming the importance of such intercellular communication and exploring the molecular mechanisms involved. These mechanisms are based both on direct physical interactions, which coordinate the cellular responses, and on the collective cell behaviour that generates an optimal environment for efficient directed migration. The recent studies have described how leader cells at the front of cell groups drive migration and have highlighted the importance of follower cells and cell-cell communication, both between followers and between follower and leader cells, to improve the efficiency of collective movement