Starts 27 Oct 2026 14:30
Ends 27 Oct 2026 15:30
Central European Time
CMSP Seminar (Atomistic Simulation Seminar Series): Small Molecule Stabilization of Proteins and Nanoparticles: Rethinking Colloidal Stabilization
Luigi Stasi Seminar Room (Leonardo Building, 1st floor) and via Zoom
Francesco Stellacci
(Institute of Materials, and Bioengineering Institute, Ecole Polytechnique Fédérale de Lausanne, Switzerland)
ABSTRACT:
Amino acids have been used for decades in biological and pharmaceutical formulations, yet their stabilizing role is still debated and is often described in non-quantitative or protein-specific terms. In this talk, I will argue that we have been overlooking a general property: amino acids act as modulators of colloidal interactions—not just for proteins, but also for DNA and even synthetic nanoparticles.
I will begin by showing how we systematically measured the interactions between suspended particles using osmotic virial coefficients and potential of mean force. We find that the stabilizing effects of amino acids are remarkably consistent across very different systems, suggesting a broad, non-specific mechanism.
To explain this, we developed a theoretical model treating amino acids as weakly interacting small molecules binding to patchy colloidal surfaces. We put this model to the test, comparing predictions against experimental dissociation constants, and the numbers line up: for instance, with proline and lysozyme, theory and experiment agree within a factor of two. [1]
The model leads to some clear, testable predictions—like the idea that short peptides should be more effective than the same number of free amino acids, or that charged amino acids only stabilize oppositely charged proteins. We verified each of these in the lab.
Finally, I will show that these weak interactions can have strong consequences: they can suppress liquid-liquid phase separation, block stress granule formation in cells, and even double insulin’s bioavailability in mice when co-formulated with proline.
Overall, our results suggest we should think of small molecules like amino acids not just as passive ingredients but as active modulators of colloidal behavior—just as we already account for salt when studying electrostatics, we should be paying similar attention to these small molecular players.
[1] Mao, et al , Nature (2025)
I will begin by showing how we systematically measured the interactions between suspended particles using osmotic virial coefficients and potential of mean force. We find that the stabilizing effects of amino acids are remarkably consistent across very different systems, suggesting a broad, non-specific mechanism.
To explain this, we developed a theoretical model treating amino acids as weakly interacting small molecules binding to patchy colloidal surfaces. We put this model to the test, comparing predictions against experimental dissociation constants, and the numbers line up: for instance, with proline and lysozyme, theory and experiment agree within a factor of two. [1]
The model leads to some clear, testable predictions—like the idea that short peptides should be more effective than the same number of free amino acids, or that charged amino acids only stabilize oppositely charged proteins. We verified each of these in the lab.
Finally, I will show that these weak interactions can have strong consequences: they can suppress liquid-liquid phase separation, block stress granule formation in cells, and even double insulin’s bioavailability in mice when co-formulated with proline.
Overall, our results suggest we should think of small molecules like amino acids not just as passive ingredients but as active modulators of colloidal behavior—just as we already account for salt when studying electrostatics, we should be paying similar attention to these small molecular players.
[1] Mao, et al , Nature (2025)