Multiple mechanisms of 3D migration: the origins of plasticity

Abstract

Cells migrate through 3D environments using a surprisingly wide variety of molecular mechanisms. These distinct modes of migration often rely on the same intracellular components, which are used in different ways to achieve cell motility. Recent work reveals that how a cell moves can be dictated by the relative amounts of cell-matrix adhesion and actomyosin contractility. A current concept is that the level of difficulty in squeezing the nucleus through a confining 3D environment determines the amounts of adhesion and contractility required for cell motility. Ultimately, determining how the nucleus controls the mode of cell migration will be essential for understanding both physiological and pathological processes dependent on cell migration in the body.

Apicomplexan F-actin is required for efficient nuclear entry during host cell invasion

“…In addition, compressive forces, caused by the host cell at the TJ requires the deformation of the parasite during invasion, which appears to be counterbalanced to ensure integrity of the parasite (Bichet et al, 2016). In fact, the invasion of host cells through the TJ appears in many aspects very similar to the migration of eukaryotic cells through a constricted environment, with impressive morphological changes observed at the point of constriction (Petrie & Yamada, 2016). Here, the nucleus represents a physical barrier for migration that requires to be modulated, deformed and protected in order to be squeezed through the constriction (Thiam et al, 2016).…”

Microtubules in 3D cell motility

“…This, in many cases, provides a better mimic of physiological tissue environments. The assessment of adhesion and actin regulators in 3D models has already generated considerable advances in our comprehension of cytoskeletal functions within the context of 3D cell motility and the great plasticity of this process observed in vivo (Paul et al, 2015;Petrie and Yamada, 2016). The exciting new field of mechanobiology integrates matrix properties with cytoskeletal dynamics and addresses how the feedback relationships between them fine-tune cell behavior in 3D environments (Charras and Sahai, 2014).…”

“…1). Other cell migration modes in 3D matrices depend on pressure-based protrusions, such as blebs and lobopodia, but the role of microtubules in this context is poorly understood (Petrie and Yamada, 2016). Importantly, 3D cell migration in vivo displays significant plasticity that allows, in certain physiological or pathogenic situations, to switch between collective and single cell behavior (Friedl and Gilmour, 2009;Mayor and Etienne-Manneville, 2016).…”

Vesicle trafficking pathways that direct cell migration in 3D matrices and in vivo

“…However, 2D surfaces do not accurately represent three‐dimensional (3D) in vivo environments, in which cells must navigate through a plethora of obstacles, including ECM, other cells and tissue boundaries. Recent research has shifted towards investigating cell migration within environments that more closely recapitulate those present in vivo, allowing the characterization of a range of 3D migratory modes, including mesenchymal, amoeboid and lobopodial (Box ). Here, we highlight recent examples demonstrating that endosomal trafficking of cargoes, in particular adhesion receptors and RTKs, controls cell migration and invasion both in 3D microenvironments and in vivo.…”