{"doi":"10.1101/2023.10.03.560747","title":"Separation of sticker-spacer energetics governs the coalescence of metastable condensates","abstract":"Abstract Biological condensates often emerge as a multi-droplet state and never coalesce into one large droplet within the experimental timespan. Previous work revealed that the sticker-spacer architecture of biopolymers may dynamically stabilize the multi-droplet state. Here, we simulate the condensate coalescence using metadynamics approach and reveal two distinct physical mechanisms underlying the fusion of droplets. Condensates made of sticker-spacer polymers readily undergo a kinetic arrest when stickers exhibit slow exchange while fast exchanging stickers at similar levels of saturation allow merger to equilibrium states. On the other hand, condensates composed of homopolymers fuse readily until they reach a threshold density. Increase in entropy upon inter-condensate mixing of chains drives the fusion of sticker-spacer chains. We map the range of mechanisms of kinetic arrest from slow sticker exchange dynamics to density mediated in terms of energetic separation of stickers and spacers. Our predictions appear to be in qualitative agreement with recent experiments probing dynamic nature of protein-RNA condensates. Statement of significance A key conundrum of biological condensates is the coexistence of multiple droplets, in direct variance with classical predictions of mean-field theories of polymer solutions. Our current study uncovers that the merging of sticker-spacer condensate is an entropy driven process, as opposed to the surface energy driven fusion that are observed for canonical liquid droplets. This entropy, stemming from the inter-condensate polymer exchange, makes the droplet merging process dependent on inter-sticker dissociation kinetics. Stronger inter-sticker interaction triggers a kinetic arrest, preventing the condensate merger even at a low density. Our prediction starkly correlates with recent experimental findings on protein-RNA condensates in vitro and in vivo, highlighting the biological relevance of the interplay of kinetics and thermodynamics.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":395182,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9504,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":247329,"name":"Eugene I. Shakhnovich","orcid":"0000-0002-4769-2265","position":1,"is_corresponding":false},{"id":586968,"name":"Aniruddha Chattaraj","orcid":"0000-0002-7105-6621","position":0,"is_corresponding":true}],"reference_count":51,"raw_metadata":null,"created_at":"2026-07-19T01:19:18.686170Z","pmid":"37873097","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}