Disulfide Crosslink Density is a Key Determinant in the Formation, Dynamics, and Maturation of Cysteine-rich Designer Biomolecular Condensates.

Increasing cysteine density in cysteine-rich designer phase-separating peptides drives a ~60-fold drop in Csat (1.5 mM to 25 M) and reduces condensate fluidity by about an order of magnitude.

• Why it matters: Covalent disulfide crosslinks can tune condensate assembly and properties, but the sequence rules that control redox-responsive formation, maturation, and material behavior are unclear.
• What they did: The study built two peptide libraries varying inter-cysteine spacer length (2–10 residues) or cysteine density (0–33%) and measured Csat and fluidity via FRAP, including behavior across three redox cycles.
• The result: Higher cysteine densities also decreased cargo uptake of eGFP (~60% to ~9%) and TMR (~70% to ~45%), consistent with reduced mesh size and enabling design of redox-responsive, porous condensates.

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