Understanding the Effect of Secondary Structure on Molecular Interactions of Poly-l-lysine with Different Substrates by SFA

Abstract

Nonspecific adsorption of proteins on biomaterial surfaces challenges the widespread application of engineered materials, and understanding the impact of secondary structure of proteins and peptides on their adsorption process is of both fundamental and practical importance in bioengineering. In this work, poly-L-lysine (PLL)-based α-helices and β-sheets were chosen as a model system to investigate the effect of secondary structure on peptide interactions with substrates of various surface chemistries. Circular dichroism (CD) was used to confirm the presence of both α-helix and β-sheet structured PLL in aqueous solutions and upon adsorption to quartz, where these secondary structures seemed to be preserved. Atomic force microscopy (AFM) imaging showed different surface patterns for adsorbed α-helix and β-sheet PLL. Interactions between PLL of different secondary structures and various substrates (i.e., PLL, Au, mica, and poly(ethylene glycol) (PEG)) were directly measured using a surface forces apparatus (SFA). It was found that β-sheet PLL films showed higher adsorbed layer thicknesses in general. Adhesion energies of β-sheet versus Au and β-sheet versus β-sheet were considerably higher than that of α-helix versus Au and α-helix versus α-helix systems, respectively. Au and β-sheet PLL interactions seemed to be more dependent on the salt concentration than that of α-helix, while the presence of a grafted PEG layer greatly diminished any attraction with either PLL structure. The molecular interaction mechanism of peptide in different secondary structures is discussed in terms of Derjaguin-Landau-Verwey-Overbeek (DLVO) theory, Alexander-de Gennes (AdG) steric model and hydrogen bonding, which provides important insight into the fundamental understanding of the interaction mechanism between proteins and biomaterials.

Layer-by-Layer Assembly of Supported Lipid Bilayer Poly-l-Lysine Multilayers

“…We note that individual PLL peptides in the random coil conformation on lipid bilayers could not be observed with AFM, most likely because the high coverage of PLL, the diffusion of the random coil peptides, and soft interface of the lipid bilayer make the imaging of such small structures impossible. The heights of the α-helical structures are 2.8 ± 0.2 nm, in reasonable agreement with previous AFM reports of PLL on mica . Measurements of the lateral thicknesses of the filaments give values ranging from 10 to 50 nm, suggesting that many of them are in bundles, which is further evident from the large number of helices branching away from the larger bundles.…”

“…The heights of the α-helical structures are 2.8 ± 0.2 nm, in reasonable agreement with previous AFM reports of PLL on mica. 47 Measurements of the lateral thicknesses of the filaments give values ranging from 10 to 50 nm, suggesting that many of them are in bundles, which is further evident from the large number of helices branching away from the larger bundles. From a biomimetic perspective, these structures could be seen to resemble an actin cytoskeleton found at the cell membrane and at model supported membranes.…”

pH-Induced Changes in Polypeptide Conformation: Force-Field Comparison with Experimental Validation

“…The properties of PP assemblies are dictated by their properties, such as the secondary structure and charge state, in the bulk solution. For example, PLL has been reported to maintain its secondary structure upon adsorption on a quartz surface, 19 and the PLL peptide self-assembly morphology is sensitive to pH fine tuning in solution. 20 PLL adsorption has been investigated over a wide pH range with the findings revealing significant changes in the adsorption kinetics and maximal coverage of the adsorbed layer 21 as well as the surface morphology and roughness 22 as a function of solution pH.…”

Antifouling Strategies for Electrochemical Biosensing: Mechanisms and Performance toward Point of Care Based Diagnostic Applications

“…Surface coatings based on self-assembled monolayers (SAMs) of poly(ethylene glycol) (PEG) and its derivatives oligio(ethylene glycols) have been widely used in biomedical applications as PEG chains can be easily tethered to a wide range of surfaces and are both a nontoxic and nonimmunogenic polymer. 66−70 Research within the field of antifouling surface coatings has also been expanded over recent years toward alternatives to PEG and its derivatives, namely, different zwitterionic polymers, 71,72 poly(2-oxazolines), 73−76 and various biopolymers including short-chain amino acids (peptides) and glycoproteins such as lubricin (LUB). 1,77−80 The antifouling efficacy of polymer-/biopolymer-based antifouling coatings can be altered via different grafting approaches.…”

“…Surface coatings based on self-assembled monolayers (SAMs) of poly­(ethylene glycol) (PEG) and its derivatives oligio­(ethylene glycols) have been widely used in biomedical applications as PEG chains can be easily tethered to a wide range of surfaces and are both a nontoxic and non-immunogenic polymer. − Research within the field of antifouling surface coatings has also been expanded over recent years toward alternatives to PEG and its derivatives, namely, different zwitterionic polymers, , poly­(2-oxazolines), − and various biopolymers including short-chain amino acids (peptides) and glycoproteins such as lubricin (LUB). ,− The antifouling efficacy of polymer-/biopolymer-based antifouling coatings can be altered via different grafting approaches. The coatings can be “grafted-to” the electrode surface through covalent binding to create a linear polymer brush, or can be “grafted-from” the surface via surface-initiated atom transfer radical polymerization (SI-ATRP) or electropolymerization. − Typically, polymer-/biopolymer-based coatings are integrated onto the surface as linear brushes of self-assembled monolayers (SAMs), which have been shown to significantly prevent bacterial adhesion in biomedical implants .…”