Microtubules in 3D cell motility

Abstract

Three-dimensional (3D) cell motility underlies essential processes, such as embryonic development, tissue repair and immune surveillance, and is involved in cancer progression. Although the cytoskeleton is a well-studied regulator of cell migration, most of what we know about its functions originates from studies conducted in twodimensional (2D) cultures. This research established that the microtubule network mediates polarized trafficking and signaling that are crucial for cell shape and movement in 2D. In parallel, developments in light microscopy and 3D cell culture systems progressively allowed to investigate cytoskeletal functions in more physiologically relevant settings. Interestingly, several studies have demonstrated that microtubule involvement in cell morphogenesis and motility can differ in 2D and 3D environments. In this Commentary, we discuss these differences and their relevance for the understanding the role of microtubules in cell migration in vivo. We also provide an overview of microtubule functions that were shown to control cell shape and motility in 3D matrices and discuss how they can be investigated further by using physiologically relevant models.

Computational modeling of single‐cell mechanics and cytoskeletal mechanobiology

“…Molecular dynamics and coarse‐grain techniques have also been used to study microtubule growth and instability . Despite the fact that microtubules are known to play a role in cell morphogenesis and cell migration mechanics, very few mechanical models of microtubule networks have been developed. Allain et al used particles to define a discretized connected microtubule network and simulated their mechanical dynamics using Newtonian mechanics.…”

“…While there have been many studies that investigated the stiffness of intermediate filaments and microtubules, more experimental and computational studies are needed to understand the mechanisms that govern microtubule and intermediate filament network dynamics (as mentioned in Mechanics of Microtubules and Intermediate Filament Networks and Mathematical Models of Microtubules and Intermediate Filament Networks ). Their contributions to the emergent behavior of the cell cytoskeleton have also only gained increased traction recently.…”

A semi-automated machine learning-aided approach to quantitative analysis of centrosomes and microtubule organization

“…An increase in MT density and EB3 comets around amplified centrosomes reflect differences in MTs between non-amplified and amplified interphase breast cancer cells. Such altered cytoskeletal architecture could lead to changes to intracellular trafficking and disrupt important cellular processes including ciliogenesis, cell migration and cell polarization (Bouchet and Akhmanova, 2017;Caviston and Holzbaur, 2006;Siegrist and Doe, 2007).…”

Microtubule acetylation but not detyrosination promotes focal adhesion dynamics and cell migration

“…Cell migration relies on the polarization and coordinated regulation of numerous cell structures, including cytoskeletal elements and adhesive structures (Llense and Etienne-Manneville, 2015, Wolfenson et al, 2009, Gardel et al, 2010, Parsons et al, 2010. While actin plays a crucial role in the generation of forces that promote cell protrusion and cell net displacement, microtubules participate in cell front-to-rear polarization (Elric andEtienne-Manneville, 2014, Etienne-Manneville, 2013) and focal adhesion dynamics Wittmann, 2012, Etienne-Manneville, 2013) to promote astrocyte or fibroblast migration and endothelial cell invasion (Etienne-Manneville, 2004, Etienne-Manneville and Hall, 2001, Bouchet et al, 2016, Bouchet and Akhmanova, 2017. At the cell front, microtubules are captured in the vicinity of nascent adhesions and contribute to the polarized delivery of integrins towards these sites (Bretscher and Aguado-Velasco, 1998).…”