Demonstrating the significance of individual molecules during mechanical stress in cells

Newswise — The cells within our organism are in constant contact with mechanical forces, which originate from either external sources or are internally generated. The capacity to react to these mechanical stimuli is crucial for numerous biological activities. Yet, comprehending how cells effectively process such stimuli remains limited due to the absence of techniques to examine intricate mechanical signals within cells. Scientists at the University of Münster in Germany have recently devised a technique to modify the mechanics of individual molecules, enabling them to explore their roles within cells. The results of their research have been published in the scientific journal Science Advances.

Led by Prof Carsten Grashoff, a cell biologist, the team devised a technique that utilizes a light-sensitive molecule to modify proteins, which can be mechanically manipulated through brief light pulses. This innovative approach granted the scientists precise temporal and spatial control, allowing them to selectively disrupt individual proteins and explore their mechanical relevance within cells. The initial experiments shed light on the functionality of two molecules that not only play a vital role in cell adhesion but are also implicated in various diseases. One such molecule is talin, which is indispensable for facilitating the transmission of mechanical forces during cell adhesion in connective tissues, such as in the process of cell migration. On the other hand, desmoplakin, another protein investigated, is crucial for withstanding mechanical strain in cell-cell junctions prevalent in epithelial tissues like the skin. Prof Carsten Grashoff highlights the significance of these findings, stating, "Collectively, these results offer insights into how individual proteins can regulate the mechanical properties of specific cellular structures."

Since the developed technique is genetically encoded, it can be inserted into the genome at various positions. This versatility offers researchers the potential to apply the method in exploring the mechanobiological characteristics of numerous proteins in living cells, model organisms, and disease models. The researchers envision broad applicability for their innovative approach, fostering a deeper understanding of how mechanical forces impact cellular processes and opening new avenues for studying the role of proteins in various biological contexts.

Mechanical stimuli, like other types of signals, are processed within cells primarily at the level of individual proteins. Although researchers have made progress in identifying molecules that experience direct mechanical forces in cells, understanding the specific mechanical contributions of individual proteins in complex cellular processes has remained challenging. Carsten Grashoff's team conducted experiments utilizing a light-sensitive connection that retains its structural integrity under significant mechanical forces but can be broken by exposure to light radiation. Similar light-sensitive proteins are found in plants, where they play a role in light-directed orientation. By incorporating these predetermined breaking points into specific genes, such as talin and desmoplakin, using molecular biology techniques, the team generated cells from connective tissue and skin that could be precisely controlled at the level of individual proteins using a laser beam. Modulation and analysis of these living cells, derived from mouse cell culture models, were achieved using fluorescence microscopy methods. These innovative approaches provided valuable insights into the mechanical properties of proteins within cells, expanding our understanding of mechanobiology in complex biological systems.