Mechanisms Of Defective Graphene Nanomaterial Interaction With Biomolecules

With the rapid development of nanotechnology and nanoscience,nanomaterials especially carbon-based nanomaterials have been applied to the biomedical field,yielding diverse employment as drug and gene delivery platforms,cell/tissue labeling and imaging agents,tumor photothermal and photodynamic therapies,due to their extraordinary chemical and physical properties.However,the primary concern of biosafety of the nanomaterials have also attracted great research interest.When incorporating nanomaterials into biological system for practical applications,it is vital and essential to study the interactions of nanomaterials with biomolecules(such as proteins,nucleotides and membranes)at molecular and even atomic levels.On the other hand,because of the preparation process used and the environmental and operating conditions,it is inevitable that experimentally fabricated nanomaterials are imperfect and contain defects(such as local defects or wrinkles).Although the interactions between biomolecules and nanomaterials have been studied by both experimental and theoretical approaches,the contribution from defects has yet to be studied,exposing an urgent need for a comprehensive understanding of how defects influence biological interactions.In this work,using molecular dynamics simulations,we study the interaction of the local defect graphene with YAP65WW-domain and the wrinkled graphene with double-stranded DNA(dsDNA)and chicken villin headpiece subdomain protein(HP35).The results show that the local defects on graphene consistently act to unfold the YAP65WW-domain,while the simulations of protein binding on ideal graphene reveal a well-preserved native structure.This is because the charged residues in YAP65WW-domain bound to the graphene defect are tightly anchored due to favorable electrostatic interactions,while other parts of the protein can migrate freely,the movement difference acts to denature and unfold the entire protein.For the interaction of wrinkled graphene with dsDNA,we find dsDNA experiences severe structural deformation upon binding to wrinkled graphene surface,whereas it tends to maintain its native structure upon binding to idealized graphene nanosheet.Further analysis reveals it is energetically advantageous for the terminal bases to bind to wrinkled area,serving as anchors on the nanosheet.Consequently,movement of the remaining part of the dsDNA generates a "stretching" force to the anchoring bases,causing the breakage of the inter-base hydrogen bonds and local unfolding.Like a slider opening up a zipper,the local unfolding proceeds sequentially from the first base pair to the next.This zipper-like unfolding subsequently exposes more DNA bases to contact with wrinkled area,thus accelerating the dsDNA deformation.Similar unfolding events are also found in the wrinkled graphene-HP35 interaction case.These findings highlight the importance of morphology defects in the interaction of graphene with biomolecules and deepen our understanding of the influence of graphene morphology on the conformation of biomolecules.