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Shear stress is an important mechanical stimulus that plays a critical role in modulating cell functions. In this study, we investigated the regulating effects of shear stress on the internalization of cell membrane proteins in a microfluidic chip. A hairpin-type DNA probe was developed and indiscriminately anchored to the cell surface, acting as an indicator for the membrane proteins. When cells were exposed to shear stress generated from fluid cell medium containing external proteins, strong fluorescence was emanated from intracellular regions. With intensive investigation, results revealed that shear stress could enhance the specific cell endocytosis pathway and promote membrane protein internalization. This process was indicated by the enhanced intracellular fluorescence, generated from the internalized and mitochondria accumulated DNA probes. This study not only uncovered new cellular mechanotransduction mechanisms but also provided a versatile method that enabled in situ and dynamic indication of cell responses to mechanical stimuli.

Shear Stress-Enhanced Internalization of Cell Membrane Proteins Indicated by a Hairpin-Type DNA Probe