Living cells as a biological analog of optical tweezers – a non-invasive microrheology approach

Hardiman, William; Clark, Matt; Friel, Claire; Huett, Alan; Pérez-Cota, Fernando; Setchfield, Kerry; Wright, Amanda J.; Tassieri, Manlio

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 analysis to quantify changes in the cells’ low-frequency elastic modulus, G'0, and the cell’s dynamics over the time window ~10-2s to 10 s. 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.

• Journal Article Type: Article
• Acceptance Date: Apr 25, 2023
• Online Publication Date: May 1, 2023
• Publication Date: 2023-08
• Deposit Date: May 12, 2023
• Publicly Available Date: May 17, 2023
• Journal: Acta Biomaterialia
• Print ISSN: 1742-7061
• Electronic ISSN: 1878-7568
• Publisher: Elsevier BV
• Peer Reviewed: Peer Reviewed
• Volume: 166
• Pages: 317-325
• DOI: https://doi.org/10.1016/j.actbio.2023.04.039
• Keywords: Molecular Biology; Biomedical Engineering; Biochemistry; Biomaterials; General Medicine; Biotechnology
• Public URL: https://nottingham-repository.worktribe.com/output/20287297
• Publisher URL: https://www.sciencedirect.com/science/article/pii/S1742706123002398?via%3Dihub