Biomimetic Virus-Like Particles to control cell functions

Abstract

Biomimetic cues from the extracellular matrix (ECM) are essential for optimizing cell microenvironments and biomaterials. While native ECM proteins or synthetic peptides offer potential solutions, challenges such as production cost, solubility, and conformational stability limit their use. Here, we present the development of virus-like particles (VLPs) derived from the AP205 RNA phage displaying peptides from key ECM proteins and evaluate their biological activity in a variety of assays. We show that our engineered VLPs can effectively stimulate cell adhesion, migration, proliferation and differentiation. By comparing focal adhesions formed by RGD VLPs with their parent protein, fibronectin, we elucidate both similarities and differences in cell interactions. In addition, we construct heterodimeric particles co-expressing RGD with differentiation peptides and demonstrate retention of bioactivity in a multi-peptide context. This study establishes AP205 VLPs as versatile nanoscale platforms capable of tuning cell functions, with promising applications in nanomedicine and biomaterials.