Abstract
Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood. Here we use nanomechanical sensors and intact human cells to provide unique insights into the signaling pathways of connectivity networks, which deliver the ability to probe cells to produce biologically relevant, quantifiable and reproducible signals. We quantify the mechanical signals from malignant cancer cells, with 10 cells per ml in 1000-fold excess of non-neoplastic human epithelial cells. Moreover, we demonstrate that a direct link between cells and molecules creates a continuous connectivity which acts like a percolating network to propagate mechanical forces over both short and long length-scales. The findings provide mechanistic insights into how cancer cells interact with one another and with their microenvironments, enabling them to invade the surrounding tissues. Further, with this system it is possible to understand how cancer clusters are able to co-ordinate their migration through narrow blood capillaries.
Highlights
Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood
The systematic experiments on model self-assembled monolayers (SAMs) and cancer cells suggest that the hinge and mechanical connectivity play a major role in mechanotransduction
We unravel a fundamental association between signaling and mechanical connectivity network, demonstrating that capture molecules arranged parallel to the long axis of a sensing element produce a larger response than those arranged in the transverse configuration
Summary
Mechanical signaling involved in molecular interactions lies at the heart of materials science and biological systems, but the mechanisms involved are poorly understood. The sensitivity of these techniques is limited and fundamental gaps remain in our understanding of how molecules or cells collectively translate their interactions into mechanical forces By virtue of their ability to resolve forces at the level of individual hydrogen bonds[14], mechanical sensors derived from micro-fabricated silicon cantilevers could potentially provide more sensitive strategies for quantifying the mechanical forces where both physiology and pathology come into play. The high force that breast cancer cells exert on the sensor allows them to attach strongly to the surface but can help them to penetrate through narrow blood capillaries—which gives us an insight into one of the ways that cancer is able to spread throughout the body Until now it has not been clear how the network of cell-surface receptors and signaling pathways control the cell response, but our study suggests that the level of mechanical forces is locationspecific and provides mechanistic insights into how cells interact with one another. This will help to better understand how cancer cells are able to coordinate migration to different parts of the body irrespective of the microenvironment
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