Show simple item record

dc.contributor.authorGaraizar, Adiran
dc.contributor.authorEspinosa, Jorge R
dc.contributor.authorJoseph, Jerelle A
dc.contributor.authorCollepardo-Guevara, Rosana
dc.date.accessioned2022-04-19T13:17:20Z
dc.date.available2022-04-19T13:17:20Z
dc.date.issued2022-03-15
dc.identifier.issn2045-2322
dc.identifier.other35293386
dc.identifier.otherPMC8924231
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/336162
dc.description.abstractBiomolecular condensates formed by the process of liquid-liquid phase separation (LLPS) play diverse roles inside cells, from spatiotemporal compartmentalisation to speeding up chemical reactions. Upon maturation, the liquid-like properties of condensates, which underpin their functions, are gradually lost, eventually giving rise to solid-like states with potential pathological implications. Enhancement of inter-protein interactions is one of the main mechanisms suggested to trigger the formation of solid-like condensates. To gain a molecular-level understanding of how the accumulation of stronger interactions among proteins inside condensates affect the kinetic and thermodynamic properties of biomolecular condensates, and their shapes over time, we develop a tailored coarse-grained model of proteins that transition from establishing weak to stronger inter-protein interactions inside condensates. Our simulations reveal that the fast accumulation of strongly binding proteins during the nucleation and growth stages of condensate formation results in aspherical solid-like condensates. In contrast, when strong inter-protein interactions appear only after the equilibrium condensate has been formed, or when they accumulate slowly over time with respect to the time needed for droplets to fuse and grow, spherical solid-like droplets emerge. By conducting atomistic potential-of-mean-force simulations of NUP-98 peptides-prone to forming inter-protein [Formula: see text]-sheets-we observe that formation of inter-peptide [Formula: see text]-sheets increases the strength of the interactions consistently with the loss of liquid-like condensate properties we observe at the coarse-grained level. Overall, our work aids in elucidating fundamental molecular, kinetic, and thermodynamic mechanisms linking the rate of change in protein interaction strength to condensate shape and maturation during ageing.
dc.languageeng
dc.publisherSpringer Science and Business Media LLC
dc.rightsAttribution 4.0 International
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.sourcenlmid: 101563288
dc.sourceessn: 2045-2322
dc.titleKinetic interplay between droplet maturation and coalescence modulates shape of aged protein condensates.
dc.typeArticle
dc.date.updated2022-04-19T13:17:19Z
prism.issueIdentifier1
prism.publicationNameSci Rep
prism.volume12
dc.identifier.doi10.17863/CAM.83587
dcterms.dateAccepted2022-02-07
rioxxterms.versionofrecord10.1038/s41598-022-08130-2
rioxxterms.versionVoR
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0/
dc.contributor.orcidEspinosa, Jorge R [0000-0001-9530-2658]
dc.identifier.eissn2045-2322
pubs.funder-project-idEngineering and Physical Sciences Research Council (EP/P020259/1)
pubs.funder-project-idEuropean Research Council (803326)
cam.issuedOnline2022-03-15


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

Attribution 4.0 International
Except where otherwise noted, this item's licence is described as Attribution 4.0 International