Opposites attract: Crosstalk between vimentin and microtubules - mechanical stability vs. dynamic adaptability

Introduction

The cytoskeleton is mainly composed of actin, microtubules, and intermediate filaments. It is fundamentally important for many cellular processes, which is reflected in its morphological and functional diversity. In the past, in-depth analysis of actin and microtubule networks made it possible to reconstitute their diversity in vitro with astonishing precision. This enabled a detailed understanding of the mechanisms underlying actin and microtubule network formation, which are the basis for many cellular processes.

Current Knowledge Gaps

In contrast, our knowledge of intermediate filaments is still in its infancy. We are far from rebuilding complex intermediate filament networks and their interactions with other cytoskeletal elements in vitro. As intermediate filaments are a major determinant of cellular resilience against mechanical stress and their mutations associate with diseases, detailed insight into intermediate filament network formation and properties will represent a milestone in cytoskeletal research.

Project Overview

The proposed project will be a major step in this direction. We focus on vimentin, the most ubiquitous member of the intermediate filament family.

Research Objectives

We will investigate the following aspects:

1. The role of vimentin-microtubule crosstalk.
2. The relation between network morphology and mechanical stress.

Key Questions

• How do these networks provide cells with mechanical stability while being able to rapidly change their morphology?

Methodology

Through a combination of biochemical, structuring, and mechanical methods, we will address the key questions outlined above. This research is relevant in many biological systems, ranging from subcellular structures to tissues and organisms.

Expected Outcomes

In this way, CROSSTALK will pave the way towards a clearer picture of this heavily understudied cytoskeletal filament. It aims at integrated, mechanistic insight into the organization and (mechanical) functions of vimentin and its interactions with microtubules, which form the basis for understanding its role in many higher-order physiological and pathological processes.