Cordintion of Spatial an Temporal Regulation of Integrin and EGFR Signaling

细胞通过不同类别的跨膜受体将细胞外信号传递到细胞内部，从而对环境做出反应。当整合素受体被细胞外基质(ECM)组分激活以介导细胞黏附时，受体酪氨酸激酶(如表皮生长因子受体(EGFR))被特定的多肽配体激活。这些不同信号的整合决定了细胞的反应，无论是生存、增殖、分化还是迁移。我们不会孤立地研究这些信号，而是使用系统的方法来确定ECM和生长因子配体的空间和时间呈现如何协同激活它们的受体并触发下游信号通路。使用一种新的纳米光刻技术，我们能够以纳米精度定位黏附相关配体的锚点，从而允许整合素沿细胞膜的接触的空间控制。这些配基图案也可以转移到机械可膨胀弹性体底物上，从而允许配基距离的动态变化。利用这个实验系统，我们将研究细胞外基质的化学结构如何影响生长因子信号，反之亦然，固定化的生长因子如EGF如何调节整合素聚集和焦点黏附组装，最终以协调的方式调节细胞反应。

Cells respond to their environment by transmitting extracellular signals to the inside of the cell via different classes of transmembrane receptors. While integrin receptors are engaged by extracellular matrix (ECM) components to mediate cell adhesion, receptor tyrosine kinases such as the epidermal growth factor receptor (EGFR) are activated by specific peptide ligands. The integration of these different signals determines the cellular response, whether it be survival, proliferation, differentiation, or migration. Rather than studying these signals in isolation, we will employ a systematic approach to determine how the spatial and temporal presentation of ECM and growth factor ligands cooperate to activate their receptors and trigger downstream signaling pathways. Using a novel nanolithographic technique we are able to position anchor points for adhesion relevant ligands with nanometer precision, allowing the spatial control of integrin engagement along the cell membrane. These ligand patterns can also be transferred onto mechanical expandable elastomer substrates, which allow the dynamic variation of the ligand distance. Using this experimental system, we will study how the chemical structure of the ECM impacts on growth factor signaling and, vice versa, how immobilized growth factors like EGF modulate integrin clustering and focal adhesion assembly, ultimately regulating cellular responses in a coordinated fashion.