Drug-induced changes of cytoskeletal structure and mechanics in fibroblasts: an atomic force microscopy study

Biophys J. 2000 Jan;78(1):520-35. doi: 10.1016/S0006-3495(00)76614-8.

Abstract

The effect of various drugs affecting the integrity of different components of the cytoskeleton on the elasticity of two fibroblast cell lines was investigated by elasticity measurements with an atomic force microscope (AFM). Disaggregation of actin filaments always resulted in a distinct decrease in the cell's average elastic modulus indicating the crucial importance of the actin network for the mechanical stability of living cells. Disruption or chemical stabilization of microtubules did not affect cell elasticity. For the f-actin-disrupting drugs different mechanisms of drug action were observed. Cytochalasins B and D and Latrunculin A disassembled stress fibers. For Cytochalasin D this was accompanied by an aggregation of actin within the cytosol. Jasplakinolide disaggregated actin filaments but did not disassemble stress fibers. Fibrous structures found in AFM images and elasticity maps of fibroblasts could be identified as stress fibers by correlation of AFM data and fluorescence images.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3T3 Cells
  • Actins / metabolism
  • Animals
  • Antineoplastic Agents / pharmacology
  • Bridged Bicyclo Compounds, Heterocyclic / pharmacology
  • Cell Line
  • Colchicine / pharmacology
  • Cytochalasin B / pharmacology
  • Cytochalasin D / pharmacology
  • Cytoskeleton / drug effects
  • Cytoskeleton / ultrastructure*
  • Demecolcine / pharmacology
  • Depsipeptides*
  • Elasticity
  • Fibroblasts / cytology
  • Fibroblasts / drug effects
  • Fibroblasts / ultrastructure
  • Kinetics
  • Marine Toxins / pharmacology
  • Mice
  • Microscopy, Atomic Force / methods
  • Microscopy, Fluorescence / methods
  • Microtubules / drug effects
  • Microtubules / ultrastructure
  • Paclitaxel / pharmacology
  • Peptides, Cyclic / pharmacology
  • Rats
  • Stress, Mechanical
  • Thiazoles / pharmacology
  • Thiazolidines

Substances

  • Actins
  • Antineoplastic Agents
  • Bridged Bicyclo Compounds, Heterocyclic
  • Depsipeptides
  • Marine Toxins
  • Peptides, Cyclic
  • Thiazoles
  • Thiazolidines
  • jasplakinolide
  • Cytochalasin D
  • Cytochalasin B
  • Paclitaxel
  • Colchicine
  • latrunculin A
  • Demecolcine