作者：Weiyi; Qian; Apratim; Bajpai; Jie; Ton...aaaultrasoundtweezerstriggermechanicaldynamicscellmechanophenotyping
摘要：Cells actively modulate mechanobiological circuitry against external perturbations to stabilize whole cell/tissue physiology.The dynamic adaption of cells to mechanical force is critical for cells to perform vital biological functions,from single cell migration to embryonic development.Dysregulation of such dynamics has been associated with pathophysiological conditions in cardiovascular diseases,cancer,aging,and developmental disorders[1].Therefore,a direct understanding of cell’s biomechanical adaptive/maladaptive behaviors and the trigger factors causing the transformation of healthy adaption to maladaptation can help reveal the regulatory role of single cell mechanosensitive dynamics in the progression of various degenerative diseases and aging.However,current efforts for uncovering fundamental associations between disease and cell architecture have been focusing on'static'measurements of biophysical properties,which is limited by the requirement of large sample sizes to obtain statistically significant data.We therefore developed a single and highly integrated platform with mechanical stimulation and fine spatiotemporal sensing functions to probe the single cell mechanical dynamics at subcellular level to determine cell’s mechanophenotypes in healthy and disease conditions.We developed an integrated micromechanical system composed of an’ultrasound tweezer’stimulator[2]and a PDMS micropillar array [3] cellular force sensor to in situ noninvasively probe and monitor single cell mechanical dynamics.Vascular smooth muscle cells(VSMCs)from healthy mouse and mouse with induced abdominal aorta aneurysm(AAA)were used for cell mechanobiological study.An ultrasound transducer(V312-SM,Olympus)was used to generate ultrasound pulses to excite lipid-encapsulated microbubbles(Targeson)binding to cell membrane through an RGD-integrin linkage to apply a transient nanonewton force to VSMCs seeded on the PDMS micropillar array.PDMS micropillar array was fabricated and functionalized as previously described [3] and acts
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