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Multivalency Enables Signal Processing at Single Protein Level.

Xiaoyu Wu1, Yuanqi Jia1, Tong Zhang2

  • 1School of Life Sciences, Westlake University, Hangzhou 310030, China.

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|October 15, 2025
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Summary
This summary is machine-generated.

We developed a computational model to design multivalent protein binders for precise cell targeting. This tool guides the creation of binders that can sense cell surface antigen identity and density for selective cell interactions.

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Area of Science:

  • Biotechnology
  • Molecular Engineering
  • Synthetic Biology

Background:

  • Synthetic signal processing in cells can utilize complex molecular networks or simpler single-molecule mechanisms.
  • Single-molecule processors offer reduced genetic load and easier delivery, with multivalent protein binders exhibiting unique behaviors based on cell antigen profiles.

Purpose of the Study:

  • To address the lack of quantitative methods for designing multivalent interactions on cell surfaces.
  • To develop a computational tool for guiding the design of multivalent proteins for cell surface binding and signal processing.

Main Methods:

  • Development of the Multivalent Antigen Sensing Simulator (MASS) computational model.
  • Validation of the MASS model through in vitro and cell binding experiments.

Main Results:

  • The MASS model accurately predicted the design of multivalent binders for sensing cell surface antigen identities and enabling selective cell killing.
  • Experimental verification confirmed the model's ability to capture the nonmonotonic relationship between valency and monovalent affinity in sensing antigen densities.
  • The model demonstrated predictive accuracy in designing binders that simultaneously sense both antigen identity and density.

Conclusions:

  • The developed MASS model provides practical guidelines for designing multivalent proteins with specific cell-sensing capabilities.
  • The simulator enables rapid and precise in silico prescreening of multivalent protein binders for various applications.