Natural
proteins such as bovine serum albumin (BSA) are readily
extracted from biological fluids and widely used in various applications
such as drug delivery and surface coatings. It is standard practice
to dope BSA proteins with an amphipathic stabilizer, most commonly
fatty acids, during purification steps to maintain BSA conformational
properties. There have been extensive studies investigating how fatty
acids and related amphiphiles affect solution-phase BSA conformational
properties, while it is far less understood how amphipathic stabilizers
might influence noncovalent BSA adsorption onto solid supports, which
is practically relevant to form surface coatings. Herein, we systematically
investigated the binding interactions between BSA proteins and different
molar ratios of caprylic acid (CA), monocaprylin (MC), and methyl
caprylate (ME) amphiphilesall of which have 8-carbon-long,
saturated hydrocarbon chains with distinct headgroupsand resulting
effects on BSA adsorption behavior on silica surfaces. Our findings
revealed that anionic CA had the greatest binding affinity to BSA,
which translated into greater solution-phase conformational stability
and reduced adsorption-related conformational changes along with relatively
low packing densities in fabricated BSA adlayers. On the other hand,
nonionic MC had moderate binding affinity to BSA and could stabilize
BSA conformational properties in the solution and adsorbed states
while also enabling BSA adlayers to form with higher packing densities.
We discuss physicochemical factors that contribute to these performance
differences, and our findings demonstrate how rational selection of
amphiphile type and amount can enable control over BSA adlayer properties,
which could lead to improved BSA protein-based surface coatings.