Live Cell Interferometry Reveals Cellular Dynamism During Force Propagation

Abstract

Cancer and many other diseases are characterized by changes in cell morphology, motion, and mechanical rigidity. However, in live cell cytology, stimulus-induced morphologic changes typically take 10-30 min to detect. Here, we employ live-cell interferometry (LCI) to visualize the rapid response of a whole cell to mechanical stimulation, on a time scale of seconds, and we detect cytoskeletal remodeling behavior within 200 s. This behavior involved small, rapid changes in cell content and miniscule changes in shape; it would be difficult to detect with conventional or phase contrast microscopy alone and is beyond the dynamic capability of AFM. We demonstrate that LCI provides a rapid, quantitative reconstruction of the cell body with no labeling. This is an advantage over traditional microscopy and flow cytometry, which require cell surface tagging and/or destructive cell fixation for labeling.

Cytoskeleton and plasma-membrane damage resulting from exposure to sustained deformations: A review of the mechanobiology of chronic wounds

“…by self-repair. dynamics of the cells' PM fluctuations has also been identified through optical and mechanical interferometry [19,20] . To evaluate effects of deformations, disruptions to cell structures were externally induced in many different ways.…”

Mechanoprofiling on membranes of living cells with atomic force microscopy and optical nano-profilometry

“…For example, digital holographic microscopy can be used to measure cell thickness and volume, provided that the refractive indices of the cytoplasm can be determined with additional optical information [26,27]. A technique called live-cell interferometry has been used to study the variations of cellular thickness under the stimulation of external force [28]. Phase-shifted laser feedback interference microscopy has also been used to measure the topography of fixed and living cells [29].…”

Cantilevers for biological monitoring: opportunities for classical and quantum physics

“…However, for future application, a different analysis may be used. The monitored low-frequency mechanical fluctuations are believed to arise from various different metabolic processes, such as cell membrane remodelling [30,[64][65][66][67]. However, the exact origins of the fluctuations are still subject of scientific debate.…”