Preparation And Application Of A Dipeptide Modified Polyethylenimine Interface Materials With Tunable Stiffness

With the development of modern medicine,more and more artificial implant materials have been widely applied in biological,medical and their related fields.Interactions between biological systems and artificial materials normally occur at their interface.Therefore,the physical and chemical properties of the interface are important factors to ensure the biocompatibility as well as realize the function of the materials.Surface stiffness is an attracting feature for designing high-performance implantable materials and artificial extracellular matrix,due to its significant impact on cell behaviors.A big challenge,and a new promising direction,is how to dynamically and reversibly modulate materials stiffness,particularly in vivo.Currently,the most frequent method for stiffness modulation,is realized by tuning the crosslinking densities of hydrogels,which has several advantages,such as good biocompatibility,high water content and large regulating range over several orders of magnitude from extremely soft to stiff.However,tuning the crosslinking densities of hydrogels will inadvertently lead to other changes in properties,such as chemical composition,shape,solubility and surface charge,which may bring potentially confounding effects.In addition,the mechanical properties of these materials cannot be changed easily once they are prepared.Smart materials also provide a new opportunity for dynamic manipulation of materials stiffness through external stimuli,such as electric field,UV light irradiation and ion.However,the introduction of external physical and chemical stimuli makes such responsive system fail to dynamically modulate the stiffness of biomaterials in vivo,a mild and high-effeicent manipulating method is always required.In this respect,nature has inspired us a lot,biological systems prefer to utilize weak interaction,particularly the stereoselective hydrogen bonding(H-bonding)interaction,to solve the problems of biomolecule interaction.The non-covalent bonding between sugar and protein,as the basis of many biomolecular recognition events,participates in numerous life activities.Therefore,how to utilize non-covalent bonding between sugar-oligopeptide as driving force to regulate materials stiffness,and thus develop stiffness controllable impant materials and devices with good biocompatibility,mild regulatory condition,which provides a new strategy for the design and development of smart materials.In this study,we prepared a smart polymer film,which was consisted of polyethylenimine grafted with oligopeptide units,and utilized non-covalent bonding between sugar-oligopeptide as driving force to regulate materials stiffness.Furthermore,the underlying molecular mechanism of such regulation,and application potential of this smart polymer film materials in the aspects of determination the enantiomeric composition,regulation of cell behaviors and separation of saccharides.The main research contents are as follows:1.Combining with main research characteristic on chiral materials of our group,we prepared a smart polymer thin film,which was consisted of flexible polyethylenimine(PEI)grafted with dipeptide units(e.g.,?-D-Asp-D-Phe,denoted as D-DF).This chiral polymer film(denoted as PEI-g-D-DF)exhibited distinct adsorption behaviors toward the ribose enantiomers.The adsoption of L-ribose induced substantial expansion of the polymer film accompanied by an obvious increase in viscoelasticity and a reduction in stiffness.Contrastingly,the adsorption of D-ribose induced substantial contraction and rigidness of the polymer film.These changes were clearly observed using atomic force microscopy(AFM)in peak force quantitative nanomechanical(PFQNM)mode.2.Then,we explained this stiffness transformation of PEI-g-D-DF by a series of experiments including a fluorescence titration experiment,a hydrogen nuclear magnetic resonance titration experiment,a bioattenuated total reflectance Fourier transform infrared experiment and quantum chemistry calculations.And a possible mechanism is proposed for explaining the stiffness regulation.The added L-ribose preferred to combine with the dipeptideunit and destroyed the initial H-bond network constructed by the dipeptide units and PEI chains.This resulted in the collapse of the H-bond network and a swollen polymer film accompanied by a substantial reduction in surface stiffness.In contrast,the distance between two polymer chains was shortened because of the “bridging” effect generated by the D-ribose guest.This shortening strengthened the H-bond network and induced shrinkage of the polymer film,leading to a substantial increase in surface stiffness.3.Taking advantages of highly specific chiral interaction and smart conformation transition of the polymer chains,chiral recognition signals of monosaccharides are captured,amplified and finally transferred to pronounced changes in the mechanic properties of a polymer film.Based on this,we developed a new method for determining the enantiomeric composition of L/D-ribose mixture.Specifically,a PEI-g-D-DF film was treated using an L/D-ribose mixture with different ee values ranging from-100% to 100%;AFM in PFQNM mode was then used to record the corresponding mean Young's modulus.The film became more rigid as the D-ribose proportion increased.The mean modulus varied linearly with the ee value of the L/D-ribose mixture,indicated that surface stiffness became a parameter for sensing the molecular chirality.To test the accuracy of this curve,we calculated the ee values of three unknown samples,and low ee errors ranged between 3 and 5% according to the calibration curve.Moreover,based on the stiffness transition of the polymeric film,the adhesion behaviors and morphologies of ES-2(a typical fibroblast cells)on the polymer surfaces,were controlled by L/D-ribose.4.Since PEI-g-D-DF displayed excellent stereoselective and chemoselective discrimination for sugar,we then prepared chromatographic stationary phases by grafting PEI-g-D-DF onto silica gels.The chiral chromatographic column is capable of separating deoxyribose racemates,as well as the separation of diverse mono-,di-,and oligosaccharides.