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The form and function of biomolecular condensates are intimately linked to their material properties. Here, we integrate microrheology with molecular simulations to dissect the physical determinants of condensate fluid phase dynamics. By quantifying the timescales and energetics of network relaxation in a series of heterotypic viscoelastic condensates, we uncover distinctive roles of sticker motifs, binding energy, and chain length in dictating condensate dynamical properties. We find that the mechanical relaxation times of condensate-spanning networks are determined by both intermolecular interactions and chain length. We demonstrate, however, that the energy barrier for network reconfiguration, termed flow activation energy, is independent of chain length and only varies with the strengths of intermolecular interactions. Biomolecular diffusion in the dense phase depends on a complex interplay between viscoelasticity and flow activation energy. Our results illuminate distinctive roles of chain length and sequence-specific multivalent interactions underlying the complex material and transport properties of biomolecular condensates.
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http://dx.doi.org/10.1126/sciadv.adi6539 | DOI Listing |
J Immunother Cancer
September 2025
Cellular Immunotherapy Program, Massachusetts General Hospital, Boston, Massachusetts, USA
Background: Tumor heterogeneity and antigen escape are mechanisms of resistance to chimeric antigen receptor (CAR)-T cell therapy, especially in solid tumors. Targeting multiple antigens with a unique CAR construct could be a strategy for a better tumor control than monospecific CAR-T cells on heterogeneous models. To overcome tumor heterogeneity, we targeted mesothelin (meso) and Mucin 16 (MUC16), two antigens commonly expressed in solid tumors, using a tandem CAR design.
View Article and Find Full Text PDFAnn Vasc Surg
September 2025
Division of Vascular Surgery, 1(st) Surgical Department, Faculty of Health Sciences, Aristotle University, Papageorgiou General Hospital, Thessaloniki, Greece.
Introduction: Nitides™ (Alvimedica, Istanbul, Turkey) is a novel polymer-free stent, which elutes Amphilimus™; a combination of sirolimus and long chain fatty acids. Aim of this prospective single-center study is to assess the efficacy and 12-months outcomes of patients with femoropopliteal arterial disease, who underwent successful angioplasty with implantation of Amphilimus™-eluting stents Nitides™.
Methods: Patients with peripheral arterial disease who underwent angioplasty of the femoropopliteal segment with DES Nitides™ from August 2021 to February 2024 were included in the study.
J Biol Chem
September 2025
Key Laboratory of Systems Health Science of Zhejiang Province, School of Life Science, Hangzhou Institute for Advanced Study, Hangzhou 310024; University of Chinese Academy of Sciences, China. Electronic address:
Phage display libraries of human single-chain variable fragments (scFv) serve as a valuable resource for generating fully human antibodies for scientific and clinical applications. In this study, we designed and constructed a highly diverse semi-synthetic humanized scFv phage display library using an optimized Kunkel mutagenesis approach. Our optimizations eliminated residual template, enhancing mutagenesis efficiency and expanding library diversity with a reservoir capacity exceeding 10.
View Article and Find Full Text PDFAm J Hum Genet
September 2025
Stanley Manne Children's Research Institute, Ann & Robert H. Lurie Children's Hospital of Chicago, Chicago, IL 60611, USA; Department of Pediatrics and Department of Cell and Developmental Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. Electronic address: erid
Fetal brain anomalies identified by prenatal ultrasound and/or magnetic resonance imaging represent a considerable healthcare burden with ∼1-2/1,000 live births. To identify the underlying etiology, trio prenatal exome sequencing or genome sequencing (ES/GS) has emerged as a comprehensive diagnostic paradigm with a reported diagnostic rate up to ∼32%. Here, we report five unrelated families with six affected individuals that presented neuroanatomical, craniofacial, and skeletal anomalies, all harboring rare, bi-allelic deleterious variants in SNAPIN, which encodes SNARE-associated protein.
View Article and Find Full Text PDFChem Sci
August 2025
Department of Chemistry, Indian Institute of Technology Bombay Powai Mumbai - 400076 India
The supramolecular organization of functional molecules at the mesoscopic level influences their material properties. Typically, planar π-conjugated (disc- or linear-shaped) molecules tend to undergo one-dimensional (1D) stacking, whereas two-dimensional (2D) organization from such building blocks is seldom observed in spite of their technological potential. Herein, we rationally achieve both 1D and 2D organizations from a single planar, π-conjugated molecular system competitive interactions.
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