title: Actin filaments play a primary role for structural integrity and viscoelastic response in cells.
abstract: This atomic force microscopy (AFM) study is devoted to the analysis of the mouse ovarian cancer cell's cytoskeleton components and the impact of both actin and microtubulin filaments on a cell's deformation behavior. Early stage, non-tumorigenic cancer cells show abundant well-organized cytoskeletal structures consisting of both actin and microtubule filaments. In sharp contrast, cells representing late and more aggressive stages of cancer display highly disorganized actin and microtubule structures. With the use of actin microfilament targeting drugs, together with the suberoylanilide hydroxamic acid (SAHA) and tubastatin A anti-cancer drugs, we modified the cell architectural framework and performed nano-indentation tests to evaluate cell elasticity and viscosity as a function of each biopolymer's weighted presence. Results demonstrate that both mechanical properties are heavily influenced by the levels and organization state of actin microfilaments; decreasing the actin organization of cells results in 85% and 79% decrease in cell elasticity and viscosity, respectively. In contrast, microtubule organization was shown to exert only marginal effects on either property. Furthermore, the anti-cancer drug, SAHA, was shown to exert little impact on the viscoelastic response of cancer cells. Finally, we report for the first time that tubastatin A, a specific HDAC6 inhibitor, increased cell elasticity as revealed by AFM tests without exerting drastic changes to the actin microfilament or microtubule networks. Our findings raise interest in a potential HDAC6 target that affects cellular mechanics just as effectively as the conventionally known cytoskeleton components.
authors.affiliation: Department of Mechanical Engineering, 100 Randolph Hall, Blacksburg, VA, USA. anketene@vt.edu
authors.forename: Alperen N
authors.initials: AN
authors.lastname: Ketene
authors.forename: Paul C
authors.initials: PC
authors.lastname: Roberts
authors.forename: Amanda A
authors.initials: AA
authors.lastname: Shea
authors.forename: Eva M
authors.initials: EM
authors.lastname: Schmelz
authors.forename: Masoud
authors.initials: M
authors.lastname: Agah
mesh_terms: D008841:Actin Cytoskeleton; D000818:Animals; D002460:Cell Line; D003599:Cytoskeleton; D055119:Elastic Modulus; D005260:Female; D040542:Mechanotransduction, Cellular; D051379:Mice; D010051:Ovarian Neoplasms / Q000503:physiopathology*; D014783:Viscosity