Silk‐Derived Protein Molecular Weight Distribution Drives Differentiated Epithelial Cell Wound Closure and Substrate Adhesion Responses, In Vitro

Abstract Silk‐derived protein (SDP) is a fibroin hydrolysate that has been found to increase corneal epithelial cell migration rates in vitro and enhances corneal tissue regeneration in vivo, however, the mechanism of these bioactive effects is unclear. Previous work has shown that selecting specific molecular weight distributions (MWD) of the fibroin hydrolysate can impact its bioactivity. In this study, the effects of high (H − ) and low molecular weight (L − ) SDP fractions on human corneal limbal‐epithelial cell viability, absorption, migration, attachment, and TGF‐β signaling are characterized. Interestingly, L‐SDP significantly increased cell migration and proliferation to accelerate wound closure rate, while the presence of TGFβRI inhibitor attenuated its activity. In contrast, H‐SDP significantly decreased migration while increasing substrate adhesion, also down‐regulating TGF‐β mRNA levels. These findings demonstrate SDP's bioactivity can be tailored to govern cellular migration or adhesion by selecting a MWD which is optimal for a specific application.