这项工作报告了一种附加环肽的自组装支架，该支架可识别膜蛋白 EGFR 并通过组装诱导聚集通过多价相互作用阻止 EGFR 信号传导。当与细胞一起孵育时，PAD-1 寡聚物首先识别癌细胞膜上过度表达的 EGFR，以阻止 EGFR，然后通过内吞作用启动细胞摄取。 PAD-1 和 EGFR 在溶酶体中的积累导致纳米纤维的形成，从而导致溶酶体膜透化 (LMP)。这些过程破坏 EGFR 的稳态并抑制 EGFR 下游信号转导以促进癌细胞存活。此外，LMP 诱导蛋白质聚集体的释放，从而产生内质网 (ER) 应激，导致癌细胞选择性死亡。体内研究表明 PAD-1 在荷瘤小鼠中具有高效的抗肿瘤功效。作为第一个例子，这项工作提供了一种控制蛋白质行为以调节活细胞中细胞事件的替代策略。

This work reports a cyclic peptide appended self-assembled scaffold that recognizes the membrane protein EGFR and arrests the EGFR signaling through multivalent interactions by assembly-induced aggregation. When incubated with cells, the oligomers of PAD-1 first recognize the overexpressed EGFR on cancer cell membranes for arresting EGFR, which then initiates cellular uptake through endocytosis. The accumulation of PAD-1 and EGFR in the lysosome results in the formation of nanofibers, leading to the lysosomal membrane permeabilization (LMP). These processes disrupt the homeostasis of EGFR and inhibit the downstream signaling transduction of EGFR for cancer cell survival. Moreover, LMP induced the release of protein aggregates that could generate endoplasmic reticulum (ER) stress, resulting in cancer cell death selectively. In vivo studies indicate the efficient antitumor efficiency of PAD-1 in tumor-bearing mice. As a first example, this work provides an alternative strategy for controlling protein behavior for tuning cellular events in living cells.