Predictions of Pattern Formation in Amino Acid Adlayers at the In Vacuo Graphene Interface: Influence of Termination State

Abstract

Controlled self‐assembly of biomolecules on graphene offers a pathway for realizing its full potential in biological applications. Microscopy has revealed the self‐assembly of amino acid adlayers into dimer rows on nonreactive substrates. However, neither the spontaneous formation of these patterns, nor the influence of amino acid termination state on the formation of patterns has been directly resolved to date. Molecular dynamics simulations, with the ability to reveal atomic level details and exert full control over the termination state, are used here to model initially disordered adlayers of neutral, zwitterionic, and neutral–zwitterionic mixtures for two types of amino acids, tryptophan and methionine, adsorbed on graphene in vacuo. The simulations of the zwitterion‐containing adlayers exhibit the spontaneous emergence of dimer row ordering, mediated by charge‐driven intermolecular interactions. In contrast, adlayers containing only neutral species do not assemble into ordered patterns. It is also found that the presence of trace amounts of water reduces the interamino acid interactions in the adlayers, but does not induce or disrupt pattern formation. Overall, the findings reveal the balance between the lateral interamino acid interactions and amino acid–graphene interactions, providing foundational insights for ultimately realizing the predictable pattern formation of biomolecules adsorbed on unreactive surfaces.

Side-chain effects on the co-existence of emergent nanopatterns in amino acid adlayers on graphene

“…48,49 For all systems, we modelled three different types of adlayers, similar to the models used in earlier work. 27 The first and second types of adlayers featured 200 amino acids either purely in the charge-neutral (N) state or the zwitterionic (Z) state, herein referred to as pure adlayers, whereas the third type of adlayer was composed of a mixture of 100 neutral molecules and 100 zwitterionic molecules, herein denoted as the mixed adlayer. The L-chiral forms of His and Ala were modelled with the neutral state capped by the amine (NH 2 ) and carboxylic (COOH) groups at the N-and C-termini respectively, while that of the zwitterionic state were capped by charged ammonium (NH 3 + ) and carboxylate (COO − ) groups.…”

“…Notably, intermolecular interactions within amino acid adlayers have been reported to be strongly influenced by the termination state, which is based on the charges present at the N-and C-termini. 11,13,19,27 Generally, zwitterionic assembly i.e. mediated by charge-charge interactions, is experimentally considered as the construction motif for ordered patterns in amino acids adsorbed on unreactive substrates.…”

“…11,13,[17][18][19][20]24 However, a recent simulation study has demonstrated that ordered patterns may not be driven solely by charge-charge interactions, but also any type of interaction involving a charge. 27 Despite the identification of the amino acid's termination state as the primary driving force for ordering, 11,[13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28] the influence of other fundamental factors affecting pattern formation, such as the amino acid side-chains themselves, remain unclear. 17,19,29 Therefore, there is a need to further explore the spontaneous emergence of these ordered structures, in terms of the connection between the patterns formed and the different amino acid side-chain characteristics.…”

“…However, this might not always be the case, given that amino acids with distinct side-chain characteristics, for example tryptophan (Trp) and methionine (Met), have been identified to form similar canonical dimer row structures upon adsorption on unreactive surfaces. 11,17,27 By combining the outcomes of molecular simulations with existing experimental data, a more complete insight into the role of the sidechains on pattern formation can be determined, by revealing how different side-chains can influence both inter-molecule and molecule-surface interactions.…”

“…27 In this regard, reports on modelling the dynamics of amino acid adlayers on non-reactive solid surfaces in vacuum are relatively few in number. 26,27,35,42 A recent MD simulation study by Awuah and Walsh 27 reported the influence of termination state on the emergence of pattern formation in both Trp and Met adlayers at the graphene interface in vacuum. These simulations revealed the spontaneous emergence of canonical dimer row structures in zwitterionic-containing adlayers.…”