TY  - JOUR
AU  - Lenton, Samuel
AU  - Chaaban, Hussein
AU  - Khaled, Mohammed
AU  - van de Weert, Marco
AU  - Strodel, Birgit
AU  - Foderà, Vito
TI  - Insulin amyloid morphology is encoded in H-bonds and electrostatics interactions ruling protein phase separation
JO  - Journal of colloid and interface science
VL  - 683
SN  - 0021-9797
CY  - Amsterdam [u.a.]
PB  - Elsevier
M1  - FZJ-2025-00360
SP  - 1175 - 1187
PY  - 2025
AB  - Ion-protein interactions regulate biological processes and are the basis of key strategies of modulating protein phase diagrams and stability in drug development. Here, we report the mechanisms by which H-bonds and electrostatic interactions in ion-protein systems determine phase separation and amyloid formation. Using microscopy, small-angle X-ray scattering, circular dichroism and atomistic molecular dynamics (MD) simulations, we found that anions specifically interacting with insulin induced phase separation by neutralising the protein charge and forming H-bond bridges between insulin molecules. The same interaction was responsible for an enhanced insulin conformational stability and resistance to oligomerisation. Under aggregation conditions, the anion-protein interaction translated into the activation of a coalescence process, leading to amyloid-like microparticles. This reaction is alternative to conformationally-driven pathways, giving rise to elongated amyloid-like fibrils and occurs in the absence of preferential ion-protein binding. Our findings depict a unifying scenario in which common interactions dictated both phase separation at low temperatures and the occurrence of pronounced heterogeneity in the amyloid morphology at high temperatures, similar to what has previously been reported for protein crystal growth.
LB  - PUB:(DE-HGF)16
C6  - 39778472
UR  - <Go to ISI:>//WOS:001407781400001
DO  - DOI:10.1016/j.jcis.2024.12.058
UR  - https://juser.fz-juelich.de/record/1035302
ER  -