Molecular interference of fibrin's divalent polymerization mechanism enables modulation of multiscale material properties.
Molecular interference of fibrin's divalent polymerization mechanism enables modulation of multiscale material properties.
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DOI：
10.1016/j.biomaterials.2015.01.010
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发表时间：
2015-05
期刊：
影响因子：
14
通讯作者：
Barker, Thomas H.
中科院分区：
文献类型：
--
作者：
Brown, Ashley C.;Baker, Stephen R.;Douglas, Alison M.;Keating, Mark;Alvarez-Elizondo, Martha B.;Botvinick, Elliot L.;Guthold, Martin;Barker, Thomas H.
基于蛋白质的聚合物通过调节分子水平相互作用为可调节的天然生物材料提供了令人兴奋和复杂的景观。在这里，我们展示了通过纤维蛋白天然聚合机制的分子“干扰”在多个长度尺度上改变蛋白质聚合物结构和机械性能的能力。我们之前曾报道过，通过聚乙二醇化的互补“旋钮 B”模拟物接合纤维蛋白的聚合“孔 b”（也称为“b 口袋”）可以增加纤维蛋白网络的孔隙率，但同时也增加了网络的刚度，这有些矛盾。在这里，我们通过表征从分子到本体聚合物的多个长度尺度上旋钮 B 纤维蛋白相互作用的影响，探索了这种现象的可能机制基础。尽管其对纤维蛋白的单价结合亲和力较弱，但以接近结合系数 Kd 的浓度添加旋钮 B 和聚乙二醇化旋钮 B 会增加纤维蛋白网络的孔隙率，这与报道的旋钮 B 与孔 b 相互作用在促进纤维蛋白纤维横向生长中的作用一致。添加聚乙二醇化旋钮 B 会在浓度接近其 Kd 时降低单纤维蛋白纤维的延伸性，但在浓度高于其 Kd 时会增加纤维的延伸性。数据表明，这种双峰行为是由于个体贡献旋钮 B（降低纤维延伸性）和 PEG（增加纤维延伸性）所致。结合基于激光陷阱的纤维蛋白聚合物的微流变学和本体流变学分析，我们的数据强烈表明，孔 b 的接合增加了单纤维的刚度，这转化为纤维蛋白聚合物的更高的储能模量，尽管它们的孔隙率增加了。这些数据指出了通过调节单纤维力学来调节纤维蛋白聚合物机械性能的可能策略。
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 complimentary ‘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 at concentrations above its Kd. The data suggest this bimodal behavior is due to the individual contributions knob B, which decreases fiber extensibility, and PEG, which increase fiber extensibility. Taken together with laser trap-based microrheological and bulk rheological analyses of fibrin polymers, our data strongly suggests that hole b engagement increases in single fiber stiffness that translates to higher storage moduli of fibrin polymers despite their increased porosity. These data point to possible strategies for tuning fibrin polymer mechanical properties through modulation of single fiber mechanics.
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影响因子：
3.7
作者：
Kotlarchyk MA;Shreim SG;Alvarez-Elizondo MB;Estrada LC;Singh R;Valdevit L;Kniazeva E;Gratton E;Putnam AJ;Botvinick EL
通讯作者：
Botvinick EL
影响因子：
2.9
作者：
Pandi, Leela;Kollman, Justin M.;Doolittle, Russell F.
通讯作者：
Doolittle, Russell F.
影响因子：
20.3
作者：
Litvinov, Rustem I.;Gorkun, Oleg V.;Weisel, John W.
通讯作者：
Weisel, John W.
影响因子：
6.1
作者：
Gong, Xing Wen;Wei, Dong Zhi;Xiong, Yu Chun
通讯作者：
Xiong, Yu Chun
影响因子：
2.9
作者：
Doolittle, Russell F.;Chen, Albert;Pandi, Leela
通讯作者：
Pandi, Leela