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Cyclic stretch and mechano-sensing

One of the less known but equally indispensible mechanical signals to form well ordered mammalian multicellular structures and organs is strain, in particular cyclic strain. Wherever tissues are contacted to pulsating blood vessels, to the intestine or the lung, cells are affected by strain of varying amplitudes and frequencies. In order to avoid straining, cells tend to reorient perpendicular to the direction of stretch. Despite the fact that just a limited number of cell types are subjected to large strain under natural conditions, mechanisms to recognize strain as well as the cellular response to this mechanical signal seem to exist and can be activated in basically every cell type. In order to analyze cellular responses to cyclic strain we developed a stretch apparatus to cyclically strain accurately calibrated elastomeric substrates that cells are adhered to.

Stretcher und ZellausrichtungIn close collaboration with our in house mechanical and electronic workshops we developed a uniaxial stretching apparatus (left) used for cyclically stretching elastomeric cell culture chambers to simulate mechanical conditions in strained tissues as e.g. arteries. As result of strain (here 14% for 16 hours) cells reorient in a well defined angle relative to the direction of applied stretch (horizontal in the right image; Cells are fibroblasts with stained actin).

We currently analyze whether and how mammalian cells respond to varying stretch speeds, stretch frequencies and amplitudes. In particular we focus on cytoskeletal and adhesion structures during reorientation and investigate how these structures adapt. We furthermore try to find out which requirements are necessary on the cellular level to allow stretch recognition with subsequent cell reorientation. We are also eager to figure out why in mammalian organisms many cells retain their cellular orientation although subjected to strain.
Every cellular response to mechanical signals is induced by a primary sensing event. Despite the high frequency of occurrence and importance of mechanosensory processes for cell function, very little is known about involved molecules and subsequent signal transduction pathways. Several mechanisms are intensively discussed as e.g. mechanosensitive ion channels or proteins with hidden binding sites that become accessible upon strain induced unfolding. Since cellular responses to cyclic stretch are very strong and well detectable on various levels after a few minutes, our stretch apparatus is an ideal system to analyze potential mechanosensitive molecules and subsequent signal transduction pathways. We combine these experiments with state of the art molecular and cell biological methods as siRNA knockdown and quantitative RT-PCR analyses or semi-quantitative live-cell fluorescent microscopy. All experiments together will allow an insight into the complex world of mechanosensing and mechanotransduction for the first time and will help to further deepen this understanding.

For further questions please contact: Dr. Bernd Hoffmann