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This computational study examines how cation-pi interactions affect the internal structure and dynamics of biomolecular condensates formed by mixtures of different peptides. Using coarse-grained simulations, researchers found that without cation-pi interactions, chemically different peptides separate into distinct regions within condensates, but adding cation-pi interactions promotes molecular mixing, enhances stability, and creates more uniform spatial and dynamic properties. The strength of cation-pi interactions can be tuned to control whether peptides mix homogeneously or segregate into core-shell architectures.
Why it matters
Understanding how specific molecular interactions control condensate organization is crucial for comprehending cellular compartmentalization and potentially designing synthetic biomolecular materials. This work reveals cation-pi interactions as a tunable mechanism to engineer condensate properties, which could inform therapeutic strategies targeting biomolecular condensates in disease.
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⚠️ Preprint – Noch nicht peer-reviewed
Dieser Artikel wurde noch nicht von unabhängigen Experten begutachtet. Die Ergebnisse sind vorläufig und sollten mit Vorsicht interpretiert werden.
Heterotypic biomolecular condensates can exhibit pronounced spatial and dynamic heterogeneity because chemically distinct components compete between self- and cross-association. Here, we use coarse-grained simulations to investigate how cation-{pi} interactions modulate this competition in condensates formed by peptides with systematic variation of hydrophobicity-to-charge ratios in binary peptide pairs. By independently tuning sequence heterogeneity, peptide composition, and cation-{pi} interaction strength, we establish how an additional short-range interaction reshapes condensate stability, internal organization, and molecular dynamics. In the absence of cation-{pi} interactions, highly heterogeneous peptide pairs form distinct core-shell architectures, with charge- and hydrophobicity-rich sequences preferentially occupying different regions of the condensate. Introducing cation-{pi} interactions progressively enhances phase stability and promotes molecular mixing, with stronger interactions substantially increasing the critical temperature and condensate density. Energetic analysis reveals that cation-{pi} interactions partially compensate for the loss of electrostatic and hydrophobic stabilization, providing an additional and tuneable source of cohesive interactions. This enhanced cross-association also suppresses spatial and dynamic heterogeneity, yielding more homogeneous peptide distributions, slower translational diffusion, and more uniform chain reconfiguration within the dense phase. Collectively, our results demonstrate that cation-{pi} interactions provide a molecular mechanism for coupling condensate stability to spatial organization and internal dynamics, enabling sequence heterogeneity and composition to be translated into distinct condensate states.