Structural control of fibrin bioactivity by mechanical deformation

Abstract

SignificanceFibrin plays a vital role in biology as the fibrous network that stabilizes blood clots and also through interaction with numerous blood components. While much is known about fibrin mechanics, comparatively little is known about how fibrin’s mechanics influence its biochemistry. We show that structural changes in fibrin under mechanical tension reduces binding of tissue plasminogen activator, an enzyme that initiates lysis. Furthermore, these structural transitions also led to decreased platelet activation through suppressed binding between platelet integrins and fibrin. Our work shows that fibrin possesses an intrinsic mechano-chemical feedback loop that regulates its bioactivity via molecular structural rearrangements.