Towards a molecular mechanism for mechanosensitive gene regulation

描述（由申请人提供）：细胞的机械微环境影响其行为，从其粘附和细胞骨架结构到其表达的基因，并已被证明影响复杂的生物过程，如干细胞分化和肿瘤进展。然而，细胞在其微环境中测量和解释机械信息的方式，特别是在发育和受伤过程中经历的瞬时机械信号，尚不清楚。当机械微环境发生改变时，本研究将通过使用力显微镜直接成像活细胞中mRNA转录物的积累和转录因子的定位来探索这些问题。通过这种方式，我们将能够破译机械刺激的阈值，包括刚度变化或力变化，以及机械输入的模式，包括连续的、振荡的和脉冲的刺激，这些都可以引发遗传反应，并改变机械输入的模式，以确定细胞如何将短暂的短时间机械输入整合到持续的长时间遗传反应中，从而使我们朝着机械敏感基因调控的详细机制发展。

DESCRIPTION (provided by applicant): A cell's mechanical microenvironment an influence its behavior, from its adhesive and cytoskeletal structure to the genes it expresses, and has been shown to affect complex biological processes such as stem cell differentiation and tumor progression. However, the manner in which a cell measures and interprets mechanical information in its microenvironment, particularly transient mechanical signals such as those experienced during development and wounding, is unclear. The proposed work will explore these questions by directly imaging the accumulation of mRNA transcripts and transcription factor localization in live cells as the mechanical microenvironment is altered using force microscopy. In this way, we will be able to decipher the thresholds of mechanical stimuli, include stiffness changes or force changes, and the patterns of mechanical inputs, including continuous, oscillatory, and pulsed stimuli, that can elicit a genetic response, and vary the patterns of mechanical inputs to determine how a cell integrates transient short-timescale mechanical inputs into sustained long-timescale genetic responses, moving us toward a detailed mechanism for mechanosensitive gene regulation.