An Acoustic Platform for Single‐Cell, High‐Throughput Measurements of the Viscoelastic Properties of Cells

Abstract

Cellular processes including adhesion, migration, and differentiation are governed by the distinct mechanical properties of each cell. Importantly, the mechanical properties of individual cells can vary depending on local physical and biochemical cues in a time‐dependent manner resulting in significant inter‐cell heterogeneity. While several different methods have been developed to interrogate the mechanical properties of single cells, throughput to capture this heterogeneity remains an issue. Here, single‐cell, high‐throughput characterization of adherent cells is demonstrated using acoustic force spectroscopy (AFS). AFS works by simultaneously, acoustically driving tens to hundreds of silica beads attached to cells away from the cell surface, allowing the user to measure the stiffness of adherent cells under multiple experimental conditions. It is shown that cells undergo marked changes in viscoelasticity as a function of temperature, by altering the temperature within the AFS microfluidic circuit between 21 and 37 °C. In addition, quantitative differences in cells exposed to different pharmacological treatments specifically targeting the membrane–cytoskeleton interface are shown. Further, the high‐throughput format of the AFS is utilized to rapidly probe, in excess of 1000 cells, three different cell lines expressing different levels of a mechanosensitive protein, Piezo1, demonstrating the ability to differentiate between cells based on protein expression levels.

Single-cell analysis reveals chemokine-mediated differential regulation of monocyte mechanics

“…A common approach used to manipulate the viscoelastic properties of cells in mechanical studies is the exposure of cells to synthetic chemicals or drugs that act on the cytoskeleton, which cause disruption of actin and tubulin filaments ( Fritzsche et al., 2017 ; Nijenhuis et al., 2014 ; Romanov et al., 2021 ; Wang et al., 2001 ; Weber et al., 2019 ). Here, we opted for an immuno-physiologically relevant approach, by exposing monocytes to one of the most important chemokines, CCL2.…”

Micropipette-based biomechanical nanotools on living cells

“…Table 2 (continued) that can be analyzed reliably (Ghassemi et al 2012;Hanson et al 2015;Jo et al 2019;Romanov et al 2021). However, there are still complementary techniques to the single cell DFS such as BFP and OT due to their bottlenecked force resolution and accuracy.…”

Passive myocardial mechanical properties: meaning, measurement, models

“…These can reveal mechanical properties across a wide spatial scale, from isolated cells, through muscle strands, sections of myocardium, to the whole heart. Recent work highlights developments for the assessment of mechanical properties at the cell level (Narasimhan et al 2020) even at high throughput (Romanov et al 2021).…”