Probing how defects in self-assembled monolayers affect protein adsorption with molecular simulation
Kayla Sprenger1, Jim Pfaendtner1
1Department of Chemical Engineering, University of Washington, Seattle, WA, 98195, USA
The formation and characterization of self-assembled monolayers, or SAMs, on solid surfaces has been extensively studied since the last half of the 20th century. The easy preparation of SAMs with different terminal groups has made their applications far-reaching and numerous, including bio-related technologies such as biosensors and medical implants, nano- and microfabrication, nanodevices, and corrosion protection. Experimental microscopy studies have long shown that SAMs have high concentrations of defects; in some cases, as with the nanofabrication method of microcontact printing, naturally-occurring imperfections in the SAMs were shown to play a beneficial role in the process1. In most cases however, defects in the monolayers can have unexpected and perhaps undesirable consequences. Though molecular simulation can offer unique insights into the consequences of SAM structural imperfections and rearrangements, it has only rarely been done; limitations of small simulation cell sizes and/or insufficient sampling times have prevented the explicit exploration of defects in typical SAM modeling studies.1 Using the special enhanced sampling method of PTMetaD-WTE2,3 to circumvent these challenges, we have performed a series of molecular dynamics studies of LKa14 adsorbing on a carboxyl-terminated alkanethiol SAM with both substrate and film naturally-occurring defects incorporated to mimic experimental observations. With an idealized SAM as a control, three types of defects are introduced, namely a gold depression that creates shortened alkyl chain lengths to mimic a characteristic defect in the underlying gold substrate, and two characteristic film defects of chains pointed towards and away from each other, creating domain boundary effects. Binding free energies have been determined in each case as a function of temperature to elucidate the entropic and energetic penalties of the defects.
 Gannon, G.; Greer, J. C.; Larsson, A.; Thompson, D. Molecular Dynamics Study of Naturally Occurring Defects in Self-Assembled Monolayer Formation. ACS Nano 2010, 4, 921-932.
 Deighan, M.; Bonomi, M.; Pfaendtner, J. Efficient Simulation of Explicitly Solvated Proteins in the Well-Tempered Ensemble. JCTC 2012, 8, 2189-2192.
 Deighan, M; Pfaendtner, J. Exhaustively Sampling Peptide Adsorption with Metadynamics. Langmuir 2013, 29, 7999-8009.