Mechanobiology Of Ferroptotic Cancer Cells As A Novel "Eat-Me" Signal: Regulating Efferocytosis Through Layer-by-Layer Coating.

The importance of the clearance of dead cells has been shown to have a regulatory role for normal tissue homeostasis and for the modulation of immune responses. However, how mechanobiological properties of dead cells affect efferocytosis remains largely unknown. Here, we report that the Young's modulus of cancer cells undergoing ferroptosis is reduced. To modulate their Young's modulus a Layer-by-Layer (LbL) nanocoating is developed. Scanning electron and fluorescence microscopy confirmed coating efficiency of ferroptotic cells while atomic force microscopy revealed encapsulation of the dead cells, increased their Young's modulus dependent on the number of applied LbL layers which increases their efferocytosis by primary macrophages. This work demonstrates the crucial role of mechanobiology of dead cells in regulating their efferocytosis by macrophages which can be exploited for the development of novel therapeutic strategies for diseases where modulation of efferocytosis could be potentially beneficial and for the design of drug delivery systems for cancer therapy. This article is protected by copyright. All rights reserved.