Oscillatory Microrheology, Creep Compliance and Stress Relaxation of Biological Cells Reveal Strong Correlations as Probed by Atomic Force Microscopy

D.A.D Flormann,C Anton,K Kaub,J Rheinlaender,T.E Schäffer,A Janshoff,M.O Pohland,E Terriac,Y Bautz,F Lautenschläger,A Ott

doi:10.3389/fphy.2021.711860

Abstract

The mechanical properties of cells are important for many biological processes, including wound healing, cancers, and embryogenesis. Currently, our understanding of cell mechanical properties remains incomplete. Different techniques have been used to probe different aspects of the mechanical properties of cells, among them microplate rheology, optical tweezers, micropipette aspiration, and magnetic twisting cytometry. These techniques have given rise to different theoretical descriptions, reaching from simple Kelvin-Voigt or Maxwell models to fractional such as power law models, and their combinations. Atomic force microscopy (AFM) is a flexible technique that enables global and local probing of adherent cells. Here, using an AFM, we indented single retinal pigmented epithelium cells adhering to the bottom of a culture dish. The indentation was performed at two locations: above the nucleus, and towards the periphery of the cell. We applied creep compliance, stress relaxation, and oscillatory rheological tests to wild type and drug modified cells. Considering known fractional and semi-fractional descriptions, we found the extracted parameters to correlate. Moreover, the Young’s modulus as obtained from the initial indentation strongly correlated with all of the parameters from the applied power-law descriptions. Our study shows that the results from different rheological tests are directly comparable. This can be used in the future, for example, to reduce the number of measurements in planned experiments. Apparently, under these experimental conditions, the cells possess a limited number of degrees of freedom as their rheological properties change.

Highlights

The mechanical properties of cells are of great importance in a wide diversity of biological phenomena, which include cell migration [1, 2], cell differentiation [3], cell division [4], embryogenesis, and cancers [5, 6]
We show that the investigational methods of stress relaxation, creep compliance, and oscillatory microrheology are interdependent, since the parameter sets used for the description are clearly correlated
We have shown that the different deformation patterns that were applied using these different methodologies are related, which indicates that the underlying connections here need to be investigated further to be fully understood

Summary

Introduction

The mechanical properties of cells are of great importance in a wide diversity of biological phenomena, which include cell migration [1, 2], cell differentiation [3], cell division [4], embryogenesis, and cancers [5, 6]. Comparisons across techniques have revealed strong quantitative differences, even when the same parameter has been probed for the same cell type [22]. Differences in the mechanical state of the cells might be involved here. Probing on different time and length scales might result in large differences in cell responses that are accompanied by different mechanical properties. Cell deformation at small scales follows a linear description [46]. In this regime, the validity of a power-law description was found to hold for many different cell types [24]. Large-scale deformation requires a more sophisticated description, taking into account non-linear and historydependent properties [23]. Small-scale cell deformation cannot be integrated to obtain the response at larger scales [25]

Methods

Results

Discussion

Conclusion