Molecular interference of fibrin's divalent polymerization mechanism enables modulation of multiscale material properties

Biomaterials
Ashley C BrownThomas H Barker

Abstract

Protein based polymers provide an exciting and complex landscape for tunable natural biomaterials through modulation of molecular level interactions. Here we demonstrate the ability to modify protein polymer structural and mechanical properties at multiple length scales by molecular 'interference' of fibrin's native polymerization mechanism. We have previously reported that engagement of fibrin's polymerization 'hole b', also known as 'b-pockets', through PEGylated complementary 'knob B' mimics can increase fibrin network porosity but also, somewhat paradoxically, increase network stiffness. Here, we explore the possible mechanistic underpinning of this phenomenon through characterization of the effects of knob B-fibrin interaction at multiple length scales from molecular to bulk polymer. Despite its weak monovalent binding affinity for fibrin, addition of both knob B and PEGylated knob B at concentrations near the binding coefficient, Kd, increased fibrin network porosity, consistent with the reported role of knob B-hole b interactions in promoting lateral growth of fibrin fibers. Addition of PEGylated knob B decreases the extensibility of single fibrin fibers at concentrations near its Kd but increases extensibility of fibers...Continue Reading

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Citations

Feb 26, 2016·Anesthesiology·Ashley C BrownNina A Guzzetta
Oct 27, 2017·Human Molecular Genetics·Francesco BonìMatteo de Rosa
Nov 27, 2019·Macromolecular Bioscience·Iwan Vaughan RobertsNicola Tirelli
Aug 18, 2017·Drug Development Research·Kimberly Nellenbach, Ashley C Brown
May 10, 2019·APL Bioengineering·Christopher Y Leon-ValdiviesoNicola Tirelli
Jun 5, 2018·Nature Biomedical Engineering·Junnan TangKe Cheng
Mar 23, 2021·Bulletin of Mathematical Biology·Katherine J PearceMansoor A Haider
May 9, 2021·Colloids and Surfaces. B, Biointerfaces·Colleen A RoosaAshley C Brown
May 2, 2018·The Journal of Physical Chemistry. B·Biplab DuttaHuib J Bakker

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