Translating Mussel Adhesion

说明（由申请人提供）：湿气是聚合物对金属和矿物的强附着力的克星。大多数工程粘合剂聚合物需要广泛的事先表面清洗，干燥，有时甚至化学改性，以有效地粘附到极性表面。这种表面制备在体内是困难的，因为生物矿化组织和植入材料表面必须在体内水化。各种海洋生物已经进化出了非常有效的粘接湿表面的策略。本提案的总体目标是获得有关海洋粘附的机械信息，以便将其转化为硬组织恢复和修复的有效应用。虽然3,4-二羟基苯丙氨酸（Dopa）蛋白参与粘附的发现已经激发了几种新的生物医学材料，但多巴并不是唯一的生物灵感主题。这里的具体目的是利用质谱法确定磷酸丝氨酸和4-羟yarginine是否以及在多大程度上与贻贝在不同表面上的粘附相关联，表征粘附交联过程中特定的蛋白质-蛋白质相互作用，并利用表面力装置探索质量、一级序列和侧链功能化等因素如何影响mfp-1在钛和羟基磷灰石等表面上的涂层或桥接行为。生物粘合剂和密封剂在牙科和整形外科中非常需要，这不仅是为了提高与硬组织结合的强度和耐久性，也是为了解放目前的技术，特别是在牙科领域，从对高活性和有毒有机配方的依赖中解放出来。公共卫生相关性：在牙科和生物医学修复中，水是固体表面和聚合物之间真正粘附的克敌。贻贝等海洋生物的强大水下粘附力是基于一套适应性的分子和生物物理特性，这些特性将系统地转化为与医学相关的策略。

DESCRIPTION (provided by applicant): Moisture is the nemesis of strong polymer adhesion to metals and minerals. Most engineered adhesive polymers require extensive prior surface cleaning, drying, and sometimes even chemical modification for effective adhesion to polar surfaces. Such surface preparation is difficult in vivo since biomineralized tissues and implant material surfaces are necessarily hydrated within the body. Various marine organisms have evolved highly effective adhesive strategies for wet surfaces. The broad goal of this proposal is to obtain mechanistic information about marine adhesion in order to translate it into effective applications for restoration and repair of hard tissues. While the discovery of 3,4-dihydroxyphenylalanine (Dopa)-protein involvement in adhesion has already inspired several new biomedical materials, Dopa is not the only bioinspired theme. The specific aims here are to determine using mass spectrometry whether and to what extent phosphoserine and 4-hydroxyarginine are linked to mussel adhesion on different surfaces, characterize the specific protein-protein interactions during adhesive cross-linking, and to explore how factors such as mass, primary sequence, and side- chain functionalization influence the coating or bridging behavior of mfp-1 on surfaces such as titanium and hydroxyapatite using the surface forces apparatus. Bio-inspired adhesives and sealants are much needed in dentistry and orthopedics not just to improve the strength and durability of bonding to hard tissues, but also to emancipate the present technology, particularly in dentistry, from a reliance on highly reactive and toxic organic formulations. PUBLIC HEALTH RELEVANCE: In dental and biomedical restorations, water is the nemesis of true adhesion between solid surfaces and polymers. The strong underwater adhesion of marine organisms such as mussels is based on an adaptive set of molecular and biophysical properties that will be systematically translated into medically relevant strategies.