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Updated: May 21, 2026
11:11
Determination of Plasma Membrane Partitioning for Peripherally-associated Proteins
Published on: June 15, 2018
Commentary: nonspecific protein binding versus membrane partitioning: it is not just semantics
1Temple University School of Pharmacy, 3307 N. Broad Street, Philadelphia, PA, USA. swati.nagar@temple.edu
Summary
Drug sequestration in cell-based assays is primarily driven by membrane partitioning, not protein binding. Physicochemical properties like LogP can predict this sequestration, impacting drug concentration measurements.
Area of Science:
- Pharmacology
- Biophysics
- Drug Discovery
Background:
- Nonspecific binding and sequestration create discrepancies between free and total drug concentrations.
- These phenomena occur in both in vitro and in vivo settings.
- Understanding these processes is crucial for accurate drug assessment.
Purpose of the Study:
- To elucidate the primary mechanisms of drug sequestration.
- To highlight the role of membrane partitioning over protein binding.
- To demonstrate the utility of physicochemical properties in predicting drug sequestration.
Main Methods:
- Discussion of membrane partitioning principles.
- Analysis of factors influencing drug concentration within membranes.
- Comparison of membrane partitioning and membrane permeability.
Main Results:
- Membrane partitioning is identified as the principal driver of drug sequestration.
- Physicochemical properties, such as LogP, can effectively predict drug sequestration.
- Drug concentration in membranes depends on influx and efflux rates.
Conclusions:
- Membrane partitioning significantly influences drug disposition in cellular systems.
- Physicochemical properties offer a predictive tool for drug sequestration in assays.
- Distinguishing partitioning from permeability is key for understanding cellular drug behavior.
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