QCM-D Reveals Parallel Adsorption Pathways Governing Amyloid-β Binding to LRP-1.
- 1Department of Chemistry, Pomona College, Claremont, California91711, United States.
Abstract
The interaction of amyloid-β (Aβ) with the low-density lipoprotein receptor-related protein-1 (LRP-1) plays a central role in amyloid clearance, yet the molecular mechanism governing this interaction remains poorly understood. Here, quartz crystal microbalance with dissipation monitoring (QCM-D) was used to investigate the adsorption kinetics of Aβ onto immobilized LRP-1 in real time. Adsorption produced a substantial decrease in resonance frequency accompanied by an increase in dissipation, consistent with the formation of a viscoelastic protein layer. Sequential washing with phosphate-buffered saline and Hellmanex III detergent revealed two populations of adsorbed Aβ that differed markedly in their resistance to removal. To distinguish between possible kinetic mechanisms, the experimental sensorgrams were fitted using competing adsorption models. A model comprising two independent parallel adsorption pathways accurately reproduced the experimental data and yielded randomly distributed residuals, whereas a sequential adsorption-rearrangement model exhibited systematic deviations characteristic of model misspecification. Analysis across a concentration series further supported the presence of two kinetically distinguishable adsorption components. Together, these results demonstrate that Aβ binding to LRP-1 is governed by heterogeneous adsorption kinetics involving parallel interaction pathways rather than a single sequential binding mechanism, providing a more realistic framework for interpreting receptor-mediated protein adsorption.
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BibTeX
@article{lewis2026qcmd,
title = {{QCM-D Reveals Parallel Adsorption Pathways Governing Amyloid-β Binding to LRP-1.}},
author = {Gabby Lewis and Elysa Tan and Yaejun Myung and Siliang Fan and Malkiat S Johal},
journal = {The journal of physical chemistry. B},
year = {2026},
month = oct,
doi = {10.1021/acs.jpcb.6c04707},
url = {https://europepmc.org/article/MED/42910872},
note = {CC BY-NC-ND},
}
RIS
TY - JOUR
TI - QCM-D Reveals Parallel Adsorption Pathways Governing Amyloid-β Binding to LRP-1.
AU - Gabby Lewis
AU - Elysa Tan
AU - Yaejun Myung
AU - Siliang Fan
AU - Malkiat S Johal
PY - 2026
DA - 2026/10/01
JO - The journal of physical chemistry. B
DO - 10.1021/acs.jpcb.6c04707
UR - https://europepmc.org/article/MED/42910872
AB - The interaction of amyloid-β (Aβ) with the low-density lipoprotein receptor-related protein-1 (LRP-1) plays a central role in amyloid clearance, yet the molecular mechanism governing this interaction remains poorly understood. Here, quartz crystal microbalance with dissipation monitoring (QCM-D) was used to investigate the adsorption kinetics of Aβ onto immobilized LRP-1 in real time. Adsorption produced a substantial decrease in resonance frequency accompanied by an increase in dissipation, consistent with the formation of a viscoelastic protein layer. Sequential washing with phosphate-buffered saline and Hellmanex III detergent revealed two populations of adsorbed Aβ that differed markedly in their resistance to removal. To distinguish between possible kinetic mechanisms, the experimental sensorgrams were fitted using competing adsorption models. A model comprising two independent parallel adsorption pathways accurately reproduced the experimental data and yielded randomly distributed residuals, whereas a sequential adsorption-rearrangement model exhibited systematic deviations characteristic of model misspecification. Analysis across a concentration series further supported the presence of two kinetically distinguishable adsorption components. Together, these results demonstrate that Aβ binding to LRP-1 is governed by heterogeneous adsorption kinetics involving parallel interaction pathways rather than a single sequential binding mechanism, providing a more realistic framework for interpreting receptor-mediated protein adsorption.
SN - 1520-6106
SN - 1520-5207
ER -