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Lipoengineering of Biomolecular Condensates Controls Material Properties and Multiphase Hierarchy to Guide Organoid
Zhiwei Huang1, Md Mahbubul Alam1, Mahtab Shokri1
1Department of Chemistry, Syracuse University, Syracuse, NY 13244, USA.
Biorxiv : the Preprint Server for Biology
|April 17, 2026
Summary
Scientists engineered biomolecular condensates using lipidation, a neutral post-translational modification. This research reveals how lipidation controls condensate properties, enabling the creation of advanced biomaterials for organoid development.
Area of Science:
- Biochemistry and Materials Science
- Investigating the role of post-translational modifications in cellular organization and biomaterial design.
Background:
- Cells utilize post-translational modifications (PTMs) to regulate biomolecular condensates, essential for cellular organization.
- While charged PTMs are understood, the impact of neutral PTMs on condensate plasticity and hierarchy is unclear.
Purpose of the Study:
- To establish design principles for controlling engineered biomolecular condensates using site-specific lipidation.
- To explore how neutral PTMs, specifically lipidation, influence condensate properties and interactions.
Main Methods:
- Systematic analysis of over 80 lipidated synthetic intrinsically disordered proteins (IDPs).
- Investigated the interplay between lipid attachment sites, local sequences, and global IDP properties.
- Engineered multi-phase architectures and hybrid hydrogels.
Main Results:
- Identified two control axes: cohesion (material state) and adhesion (miscibility/hierarchy).
- Lipidation, combined with local sequence, dictates assembly into liquids, gels, or solids.
- Lipidation and IDP scaffold properties tune heterotypic interactions and hierarchical organization.
Conclusions:
- Established a framework for rationally controlling biomolecular condensate properties via lipidation.
- Demonstrated the engineering of complex multi-phase biomaterials and functional organoids.
- Provided insights into structure-property relationships for PTMs and biomaterials.
