Tensile Stress on Microtubules Facilitates Dynein-Driven Cargo Transport

Nano Lett. 2024 Jul 31;24(30):9129-9136. doi: 10.1021/acs.nanolett.4c00209. Epub 2024 Jun 25.

Abstract

Mechanical stress significantly affects the physiological functions of cells, including tissue homeostasis, cytoskeletal alterations, and intracellular transport. As a major cytoskeletal component, microtubules respond to mechanical stimulation by altering their alignment and polymerization dynamics. Previously, we reported that microtubules may modulate cargo transport by one of the microtubule-associated motor proteins, dynein, under compressive mechanical stress. Despite the critical role of tensile stress in many biological functions, how tensile stress on microtubules regulates cargo transport is yet to be unveiled. The present study demonstrates that the low-level tensile stress-induced microtubule deformation facilitates dynein-driven transport. We validate our experimental findings using all-atom molecular dynamics simulation. Our study may provide important implications for developing new therapies for diseases that involve impaired intracellular transport.

Keywords: Cargo transport; Dynein; In vitro; Mechanical stress; Microtubule.

MeSH terms

  • Biological Transport
  • Dyneins* / chemistry
  • Dyneins* / metabolism
  • Microtubules* / chemistry
  • Microtubules* / metabolism
  • Molecular Dynamics Simulation*
  • Stress, Mechanical*
  • Tensile Strength

Substances

  • Dyneins