| Autor: |
Jarand CW; Physics Department , Tulane University , New Orleans , Louisiana 70118 , United States., Reed WF; Physics Department , Tulane University , New Orleans , Louisiana 70118 , United States. |
| Jazyk: |
angličtina |
| Zdroj: |
The journal of physical chemistry. B [J Phys Chem B] 2018 Oct 11; Vol. 122 (40), pp. 9361-9372. Date of Electronic Publication: 2018 Sep 28. |
| DOI: |
10.1021/acs.jpcb.8b07820 |
| Abstrakt: |
Is aggregation kinetics for a protein under given conditions reproducible? Is aggregation inherently deterministic, stochastic, or even chaotic? Because protein aggregation in ex vivo formulations is complex, with many origins and manifestations, the question of aggregation reproducibility for a given protein, formulation, and stressor is of both fundamental and practical significance. This work concerns temperature-induced and contact-stir-induced aggregation of bovine serum albumin (BSA) and a monoclonal antibody (mAbX). It assesses reproducibility via early-stage aggregation rates (ARs) from light scattering. "Global stressors" affect the entire protein population, for example, temperature. "Local stressors" affect only a partial population at a given instant, for example, stirring. The instrumental error distribution (IED) allows stochasticity to be identified for AR distributions (ARDs) broader than IED. For ARD at the limit of the IED, the behavior is "minimally stochastic" or "operationally deterministic." A stochastic index is defined in terms of the ratio of the standard deviation (SD) of log(AR) data and the SD of IED. Thermal aggregation was operationally deterministic for BSA and mAbX, although significant lot-to-lot variations for BSA were found. ARD from contact-stir-stress was stochastic for BSA and mAb. Despite this, log(AR) decreases logarithmically with rpm. These trends may hold for other global and local stressors. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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