Nanomechanics in Monitoring the Effectiveness of Drugs Targeting the Cancer Cell Cytoskeleton.

Andrzej Kubiak,Joanna Pabijan,Tomasz Zieliński,Małgorzata Lekka

doi:10.3390/ijms21228786

Abstract

Increasing attention is devoted to the use of nanomechanics as a marker of various pathologies. Atomic force microscopy (AFM) is one of the techniques that could be applied to quantify the nanomechanical properties of living cells with a high spatial resolution. Thus, AFM offers the possibility to trace changes in the reorganization of the cytoskeleton in living cells. Impairments in the structure, organization, and functioning of two main cytoskeletal components, namely, actin filaments and microtubules, cause severe effects, leading to cell death. That is why these cytoskeletal components are targets for antitumor therapy. This review intends to describe the gathered knowledge on the capability of AFM to trace the alterations in the nanomechanical properties of living cells induced by the action of antitumor drugs that could translate into their effectiveness.

Highlights

Atomic force microscopy (AFM) is mainly recognized as a technique applied to visualize surface topography with nano- or subnanometer resolutions
The results revealed larger deformability of bladder cancer cells than non-malignant cells
They only reach surface receptors that are indirectly linked with the cell cytoskeleton, such drugs’ action reveals significant remodeling of the targeted cells’ surface and cytoskeleton, as shown from the topographical and nanomechanical measurements realized by AFM

Summary

Introduction

Atomic force microscopy (AFM) is mainly recognized as a technique applied to visualize surface topography with nano- or subnanometer resolutions. At each point of the grid, the cantilever is moved towards the sample surface, brought in contact, and withdrawn The Oliver–Pharr model has been used to quantify the elastic modulus from the retraction part of the force curve recorded for samples, for which the indentation caused permanent, plastic deformation [24]. The limitations of these models are a lack of knowledge on the contact surface area of the indenter and lack of permanent, plastic deformation induced by the AFM tip indenting the living cells. These models are considered as two extreme limits and have opened the path to develop a unified theory describing better the interplay between a material’s adhesion and elasticity

Nanomechanical Properties of a Cell Cytoskeleton

Non-Cytoskeleton Interacting Drugs Affecting Cancer Cell Biomechanics

Biomechanics in Cancer Cell Resistance to Antitumor Drugs

Conclusions