Actin-Based Cell Protrusion in a 3D Matrix

Abstract

Cell migration controls developmental processes (gastrulation and tissue patterning), tissue homeostasis (wound repair and inflammatory responses), and the pathobiology of diseases (cancer metastasis and inflammation). Understanding how cells move in physiologically relevant environments is of major importance, and the molecular machinery behind cell movement has been well studied on 2D substrates, beginning over half a century ago. Studies over the past decade have begun to reveal the mechanisms that control cell motility within 3D microenvironments – some similar to, and some highly divergent from those found in 2D. In this review we focus on migration and invasion of cells powered by actin, including formation of actin-rich protrusions at the leading edge, and the mechanisms that control nuclear movement in cells moving in a 3D matrix.

Protein Phosphatase 1 activity controls a balance between collective and single cell modes of migration

“…Border cells with impaired Pp1 activity migrated significantly slower than control clusters (Figures 1M, 3G), suggesting that border cell motility was altered. Migrating cells form actin-rich protrusions at the front, or leading edge, which help anchor cells to the migratory substrate and provide traction for forward movement 58, 59 . In collectives, protrusive leader cells also help sense the environment to facilitate directional migration 8 .…”

“…Reduced Pp1 activity causes high levels of F-actin to redistribute from the cluster perimeter to surround entire cell cortices of individual border cells. In migrating cells, networks of F-actin produce forces essential for protrusion extension and retraction dynamics that generate forward movement 58, 59 . Further supporting a role for Pp1 in regulating F-actin, Pp1-inhibited border cells extend fewer protrusions with shorter lifetimes, resulting in altered motility patterns.…”

Periodic propagating waves coordinate RhoGTPase network dynamics at the leading and trailing edges during cell migration

“…Using a proximity ligation assay (PLA), which visualizes protein interactions in situ (Gustafsdottir et al, 2005;Soderberg et al, 2006), we measured RhoA-DIA and RhoA-ROCK complexes ( Figure 1A and 1B). Based on the commonly considered morphology of the long, narrow cell rear and the wide leading edge (Caswell and Zech, 2018), we segmented each polarized cell into three parts: the rear (about 20% of the cell length), intermediate region (next 70% of the cell length), and front (the rest 10% of the length). The density of the RhoA-effector complexes was quantified by dividing the number of PLA reactions by the area of the corresponding compartment.…”

Optogenetic control of cell morphogenesis on protein micropatterns

“…We never observed such an increase in in bleb size in non-activated cells, which produced only small, nontraveling blebs. Upon light-activation of Rac1 small blebs can be converted to lamellipodia (1) or larger blebs (2).…”