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.

Highlights

Cell migration has been well studied in 2D, but how this relates to movement in physiological 3D tissues and matrix is not clear, particularly in vertebrate interstitial matrix.

In 3D matrix cells actin polymerisation directly contributes to the formation of lamellipodia to facilitate migration and invasion (mesenchymal movement), analogous to 2D migration; actomyosin contractility promotes bleb formation to indirectly promote protrusion (amoeboid movement).

Mesenchymal migration can be characterised by polymerisation of actin to form filopodial protrusions, in the absence of lamellipodia.

Translocation of the nucleus is emerging as a critical step due to the constrictive environment of 3D matrices, and the mechanisms that transmit force to the nucleus and allow movement are beginning to be uncovered.