# The thermodynamics of protein-surface interactions

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA SANTA BARBARA · 2020 · $287,516

## Abstract

Summary. Proteins retain function when attached to some surfaces (e.g., the cell membrane) and yet very
often unfold and inactivate on others (e.g., the artificial surfaces used in many technologies). Our
understanding of why this is, however, has been hampered by a lack of quantitative methods by which we can
measure the thermodynamics of biomolecule-surface interactions. That is, despite a large body of qualitative
literature describing how adsorption alters protein structure, and a large number of empirical studies searching
for adsorption-resistant surfaces, quantitative, experimentally testable insights into how and why proteins
unfold on some surfaces and not others have proven elusive. In response, we have developed a new
experimental approach for measuring the folding free energy of biomolecules site-specifically attached to well-
defined, macroscopic surfaces (i.e., flat at the molecular length scale), including surfaces that closely mimic the
cell membrane. Comparison with bulk-solution-phase free energies then informs on the thermodynamics of the
biomolecule's interactions with the surface and, in turn, the mechanisms that drive them. Using this novel
approach we have, for the first time, accurately measured the free energy with which a simple biomolecule
interacts with a set of chemically distinct macroscopic surfaces. In parallel, we have also developed both first-
principles theory and atomistic simulation approaches that provide molecular-level structural details
unavailable to experiment alone. Leveraging these promising preliminary results we propose here the
systematic experimental, theoretical and computational study of protein-surface interactions, with our
overarching goal being to understand protein-surface interactions in sufficient detail to predict or even rationally
design protein-surface pairings supporting reversible refolding and the retention of function.

## Key facts

- **NIH application ID:** 9825547
- **Project number:** 5R01GM118560-04
- **Recipient organization:** UNIVERSITY OF CALIFORNIA SANTA BARBARA
- **Principal Investigator:** Kevin W Plaxco
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $287,516
- **Award type:** 5
- **Project period:** 2017-01-01 → 2022-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9825547

## Citation

> US National Institutes of Health, RePORTER application 9825547, The thermodynamics of protein-surface interactions (5R01GM118560-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9825547. Licensed CC0.

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