  In this work, protein-surface interactions were probed in terms of adsorption
and desorption of a model protein, bovine serum albumin, on a low-fouling
surface with single-molecule localization microscopy. Single-molecule
experiments enable precise determination of both adsorption and desorption
rates. Strikingly the experimental data show anomalous desorption kinetics,
evident as a surface dwell time that exhibits a power-law distribution, i.e. a
heavy-tailed rather than the expected exponential distribution. As a direct
consequence of this heavy-tailed distribution, the average desorption rate
depends upon the time scale of the experiment and the protein surface
concentration does not reach equilibrium. Further analysis reveals that the
observed anomalous desorption emerges due to the reversible formation of a
small fraction of soluble protein multimers (small oligomers), such that each
one desorbs from the surface with a different rate. The overall kinetics can be
described by a series of elementary reactions, yielding simple scaling
relations that predict experimental observations. This work reveals a
mechanistic origin for anomalous desorption kinetics that can be employed to
interpret observations where low-protein fouling surfaces eventually foul when
in long-term contact with protein solutions. The work also provides new
insights that can be used to define design principles for non-fouling surfaces
and to predict their performance.
