Protein aggregation is of particular interest because of its connection with many diseases and disorders. Many factors can alter the dynamics and result of this process, one of them being the diffusivity of the monomers and aggregates in the system. Here, we study experimentally and theoretically an aggregation process in cells, and we identify two distinct physical timescales that set the number and size of aggregates. The first timescale involves fast aggregation of small clusters freely diffusing in the cytoplasm, whereas in the second one, the aggregates are larger than the pore size of the cytoplasm and thus barely diffuse, and the aggregation process is slowed down. However, the process is not entirely halted, potentially reflecting a myriad of active but random forces that stir the aggregates. Such a slow timescale is essential to account for the experimental results of the aggregation process. These results could also have implications in other processes of spatial organization in cell biology, such as phase-separated droplets.
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http://dx.doi.org/10.1016/j.bpj.2021.04.032 | DOI Listing |
Background: In 2018, a nationwide survey carried out in 387 acute care hospitals from 16 out of 21 Italian regions, allowed defining an extended checklist for the participatory evaluation of person-centredness in hospital care. We aimed to validate a reduced set of core items for continuous use across the country.
Methods: Factor analysis was used to validate the construct of the checklist.
Nat Chem
January 2025
State Key Laboratory of Advanced Drug Delivery and Release Systems, Liangzhu Laboratory, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.
Vesicles play critical roles in cellular materials storage and signal transportation, even in the formation of organelles and cells. Natural vesicles are composed of a lipid layer that forms a membrane for the enclosure of substances inside. Here we report a coacervate vesicle formed by the liquid-liquid phase separation of cholesterol-modified DNA and histones.
View Article and Find Full Text PDFEMBO J
January 2025
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou University, Zhengzhou, 450000, Henan, China.
The carboxyl terminus of Hsc70-interacting protein (CHIP) is pivotal for managing misfolded and aggregated proteins via chaperone networks and degradation pathways. In a preclinical rodent model of CHIP-related ataxia, we observed that CHIP mutations lead to increased levels of phosphodiesterase 9A (PDE9A), whose role in this context remains poorly understood. Here, we investigated the molecular mechanisms underlying the role of PDE9A in CHIP-related ataxia and demonstrated that CHIP binds to PDE9A, facilitating its polyubiquitination and autophagic degradation.
View Article and Find Full Text PDFSLAS Discov
January 2025
iBET, Instituto de Biologia Experimental e Tecnológica, Apartado 12 2781-901 Oeiras, Portugal; ITQB NOVA, Instituto de Tecnologia Química e Biológica António Xavier, Av. Republica, 2780-157, Oeiras, Portugal. Electronic address:
Primary human hepatocytes (PHHs) are the preferred cell source to address liver function. Despite originating from the native tissue, one of the bottlenecks when using primary material is the donor-to-donor variability. Cryopreserved PHHs offer a high number of cells from the same donor and standardization of cell isolation and cryopreservation procedures, mitigating some of the inter-donor variability.
View Article and Find Full Text PDFProg Biophys Mol Biol
January 2025
Department of Cell Biology and Histology, Faculty of Medicine and Nursing, University of the Basque Country, UPV/EHU, Leioa 48940, Spain.
One of the most important goals of contemporary biology is to understand the principles of the molecular order underlying the complex dynamic architecture of cells. Here, we present an overview of the main driving forces involved in the cellular molecular complexity and in the emergent functional dynamic structures, spanning from the most basic molecular organization levels to the complex emergent integrative systemic behaviors. First, we address the molecular information processing which is essential in many complex fundamental mechanisms such as the epigenetic memory, alternative splicing, regulation of transcriptional system, and the adequate self-regulatory adaptation to the extracellular environment.
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