Engineered isopeptide bond stabilized fibrin inspired nanoscale peptide based sealants for efficient blood clotting

Snehasish Ghosh,Kasturee Chakraborty,Sanchita Mukherjee,Somnath Jan,Paramita Gayen,Chiranjit Dutta,Rituparna Sinha Roy,Dhananjay Bhattacharyya

doi:10.1038/s41598-017-06360-3

Abstract

Designing biologically inspired nanoscale molecular assembly with desired functionality is a challenging endeavour. Here we report the designing of fibrin-inspired nanostructured peptide based sealants which facilitate remarkably fast entrapping of blood corpuscles (~28 seconds) in contrast to fibrin (~56 seconds). Our engineered sealants are stabilized by lysine-aspartate ionic interactions and also by Nε(γ-glutamyl) lysine isopeptide bond mediated covalent interaction. Each sealant is formed by two peptides having complementary charges to promote lysine-aspartate ionic interactions and designed isopeptide bond mediated interactions. Computational analysis reveals the isopeptide bond mediated energetically favourable peptide assemblies in sealants 1–3. Our designed sealants 2 and 3 mimic fibrin-mediated clot formation mechanism in presence of transglutaminase enzyme and blood corpuscles. These fibrin-inspired peptides assemble to form sealants having superior hemostatic activities than fibrin. Designed sealants feature mechanical properties, biocompatibility, biodegradability and high adhesive strength. Such nature-inspired robust sealants might be potentially translated into clinics for facilitating efficient blood clotting to handle traumatic coagulopathy and impaired blood clotting.

Highlights

Molecular assembly serves as emerging paradigm for engineering clinically important diverse nanostructured materials[1,2,3]
Sealant 1 is formed by the self-assembly of the functional segment of human fibrinogen γ-chain, stabilized by Nε(γ-glutamyl) lysine isopeptide bond
Insertion of DAla residues imparts proteolytic stability to the sealant 326 and allows us to probe how the change in orientation of isopeptide bond can affect the sealant stability in case of sealants 2 and 3

Summary

Introduction

Molecular assembly serves as emerging paradigm for engineering clinically important diverse nanostructured materials[1,2,3]. Inspired by fibrin self-assembly mechanism and fibrin biology, we aim to design nature-inspired advanced functional biomaterials which could facilitate blood clotting more efficiently than fibrin. Such nature-inspired sealants should be biocompatible and biodegradable with minimal inflammatory response[5,6,7,8,9,10,11,12,13]. Generating rapid hemostasis from nature-inspired biodegradable hemostat material for such coagulopathic conditions will be advantageous Such hemostat materials are required to facilitate blood clotting through a mechanism independent of body’s own blood coagulation pathway to handle traumatic coagulopathy[14]

Objectives

Methods

Results