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bioRxiv · 10.64898/2026.10.09.758027

Linker stretching optimizes bonding entropy in sticker-spacer condensates

Akram, S. A.·Liu, J.·Chattaraj, A.·Gautam, S.·Chakrabarti, B.·Shakhnovich, E.·Schmit, J. D.
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Abstract

Phase separating biopolymers are often described by the sticker-spacer model, which accounts for non-attractive linkers that connect discrete attractive moieties. "Associative polymer" theories describe these systems as two coexisting fluids of stickers and spacers, respectively. In such theories the stickers and spacers are decoupled in the sense that sticker binding does not affect spacer conformations or vice versa. Informed by coarse-grained simulations, we develop a phenomenological mean-field theory to determine the microscopic coupling between the sticker and spacer degrees of freedom. Accounting for linkers connecting adjacent spacers introduces free energy contributions due to conformational entropy of the spacer and the binding combinatorics of the stickers. These contributions have opposite dependencies on spacer length because longer spacers allow a greater volume to search for binding partners but incur a greater entropy cost upon bond formation. The length dependent terms from these contributions cancel leaving a length-independent elastic term arising from the fact that a small amount of spacer stretching lowers the free energy by increasing the number of possible binding partners. The cancellation of spacer length from the theory justifies the decoupling approximation and supports mean-field treatments of heterogeneous spacers.

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Akram, S. A., Liu, J., Chattaraj, A., Gautam, S., Chakrabarti, B., Shakhnovich, E., Schmit, J. D.. 2026-10-11. Linker stretching optimizes bonding entropy in sticker-spacer condensates. https://doi.org/10.64898/2026.10.09.758027

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