Living Cells as a Biological Analog of Optical Tweezers -- a Non-Invasive Microrheology Approach

TL;DR

This paper introduces a minimally-invasive passive microrheology method to study living cells' mechanical properties over time, revealing cell stiffening during adhesion maturation and softening upon cytoskeletal disruption.

Contribution

It presents a novel non-invasive microrheology technique for live cells, enabling long-term measurement of cellular mechanics and dynamics with optical trapping analogies.

Findings

Cell stiffening observed during focal adhesion maturation.

Cell softening occurs after actin cytoskeleton disruption.

Longest duration measurement of cell stiffening to date.

Abstract

Microrheology, the study of fluids on micron length-scales, promises to reveal insights into cellular biology, including mechanical biomarkers of disease and the interplay between biomechanics and cellular function. Here a minimally-invasive passive microrheology technique is applied to individual living cells by chemically binding a bead to the surface of a cell, and observing the mean squared displacement of the bead at timescales ranging from milliseconds to 100s of seconds. Measurements are repeated over the course of hours, and presented alongside novel analysis to quantify changes in the cells' low-frequency elastic modulus and the cell's dynamics over the time window from around 0.01s to 10s. An analogy to optical trapping allows verification of the invariant viscosity of HeLa S3 cells under control conditions and after cytoskeletal disruption. Stiffening of the cell is observed during cytoskeletal rearrangement in the control case, and cell softening when the actin cytoskeleton is disrupted by Latrunculin B. These data correlate with conventional understanding that integrin binding and recruitment triggers cytoskeletal rearrangement. This is, to our knowledge, the first time that cell stiffening has been measured during focal adhesion maturation, and the longest time over which such stiffening has been quantified by any means.