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Designing Tunable DNA Condensates to Control Membrane Budding Transformation in Synthetic Cells.

Nastasja Kaletta1, Sophia Burick1,2, Yusuf Qudbuddin1

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Researchers engineered programmable DNA condensates to precisely control interactions between condensates and lipid membranes in synthetic cells. This breakthrough enables new possibilities for drug delivery and studying cellular processes.

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Area of Science:

  • Synthetic Biology
  • Biomolecular Engineering
  • Nanotechnology

Background:

  • Biomolecular condensates and lipid membranes are crucial for synthetic cell functions.
  • Controlling condensate-membrane interactions is vital for engineering synthetic cells but currently limited.
  • Existing methods lack precise control over condensate-membrane wetting behavior.

Purpose of the Study:

  • To develop programmable DNA condensates for precise control over membrane wetting.
  • To engineer tunable interactions between DNA condensates and lipid bilayers.
  • To establish a versatile platform for synthetic cell engineering and condensate-membrane dynamics studies.

Main Methods:

  • Utilized DNA Y-motifs to create programmable condensates.
  • Introduced cholesterol-functionalization to induce wetting on supported lipid bilayers (SLBs).
  • Incorporated photoactivatable DNA-lipid linkers for dynamic contact angle control via UV exposure.
  • Demonstrated selective partitioning of small unilamellar vesicles (SUVs) into DNA condensates.
  • Induced membrane wetting and outward budding in giant unilamellar vesicles (GUVs).

Main Results:

  • Programmable DNA condensates were successfully engineered to control wetting behavior.
  • Partial cholesterol-functionalization induced wetting on SLBs, unlike unmodified condensates.
  • Photoactivatable linkers allowed tunable contact angles with UV exposure.
  • Selective vesicle partitioning into condensates was achieved through programmable interactions.
  • Post-fabrication induction of condensate wetting in GUVs led to outward budding.

Conclusions:

  • Programmable DNA condensates offer a powerful platform for fine-tuning membrane-associated processes in synthetic cells.
  • This approach surpasses traditional methods relying on lipid composition or environmental changes.
  • The platform enables the design of smart drug carriers and serves as a model for studying condensate-membrane dynamics.