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Surface Engineered Biomolecular Condensates for Targeted Cell Cytotoxicity.

Chengying Yin1, Cheng Wu2,3, Xinran Yu4

  • 1Department of Ambulatory Surgery, Women's Hospital, School of Medicine, Zhejiang University, Hangzhou, 310027, China.

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Summary
This summary is machine-generated.

Engineered biomolecular condensates with a decanoic acid membrane precisely control enzyme location and activity. This enables targeted drug delivery and enhanced biocatalysis, showing potential for synthetic organelles in therapeutics.

Keywords:
biomolecular condensatescell cytotoxicityenzymatic reactionsurface engineering

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Area of Science:

  • Biomolecular engineering
  • Synthetic biology
  • Biocatalysis

Background:

  • Biomolecular condensates are key for cellular organization but lack precise interfacial control.
  • Open interfaces hinder enzymatic activity and targeted applications.

Purpose of the Study:

  • To develop a strategy for interfacial engineering of biomolecular condensates.
  • To achieve precise spatial control over biomacromolecules and modulate enzymatic activity.
  • To demonstrate the therapeutic potential of engineered condensates for targeted delivery and cell apoptosis.

Main Methods:

  • A two-step interfacial engineering strategy to form a decanoic acid membrane on decalysine/polyinosinic acid condensates.
  • Investigated molecular-weight-dependent spatial localization of biomacromolecules (≤60 kDa vs. high-molecular-weight).
  • Assessed modulated enzymatic kinetics (lipase, alkaline phosphatase) and in vitro cell co-culture delivery of alkaline phosphatase.

Main Results:

  • Decanoic acid membrane formation reduced interfacial mobility and enhanced hydrophobic molecule enrichment.
  • Achieved spatial control of biomacromolecules based on molecular weight, localizing smaller proteins inside and larger ones at the interface.
  • Demonstrated enhanced catalytic activity of interfacial alkaline phosphatase, leading to triggered release of ssDNA and significant reduction in HeLa cell viability (to 5%).

Conclusions:

  • Interfacial engineering of biomolecular condensates offers precise control over molecular localization and enzymatic function.
  • Engineered condensates serve as effective platforms for targeted biocatalysis and therapeutic delivery.
  • This approach enables functional customization of synthetic organelles for advanced biological applications.