Award Abstract # 2335597
Tools to Control and Monitor Van der Waals Forces between Nanoparticles: Quantitative Insights on Biological, Environmental, and Fungal Cell Interactions.

NSF Org: CBET
Division of Chemical, Bioengineering, Environmental, and Transport Systems
Recipient: UNIVERSITY OF CALIFORNIA, SAN DIEGO
Initial Amendment Date: January 25, 2024
Latest Amendment Date: September 17, 2024
Award Number: 2335597
Award Instrument: Continuing Grant
Program Manager: Nora Savage
nosavage@nsf.gov
 (703)292-7949
CBET
 Division of Chemical, Bioengineering, Environmental, and Transport Systems
ENG
 Directorate for Engineering
Start Date: February 1, 2024
End Date: January 31, 2027 (Estimated)
Total Intended Award Amount: $698,708.00
Total Awarded Amount to Date: $470,698.00
Funds Obligated to Date: FY 2024 = $470,698.00
History of Investigator:
  • Jesse Jokerst (Principal Investigator)
    jjokerst@ucsd.edu
Recipient Sponsored Research Office: University of California-San Diego
9500 GILMAN DR
LA JOLLA
CA  US  92093-0021
(858)534-4896
Sponsor Congressional District: 50
Primary Place of Performance: University of California-San Diego
9500 GILMAN DRIVE
LA JOLLA
CA  US  92093-0021
Primary Place of Performance
Congressional District:
50
Unique Entity Identifier (UEI): UYTTZT6G9DT1
Parent UEI:
NSF Program(s): Nanoscale Interactions Program
Primary Program Source: 01002425DB NSF RESEARCH & RELATED ACTIVIT
01002526DB NSF RESEARCH & RELATED ACTIVIT

01002627DB NSF RESEARCH & RELATED ACTIVIT
Program Reference Code(s): 7237
Program Element Code(s): 117900
Award Agency Code: 4900
Fund Agency Code: 4900
Assistance Listing Number(s): 47.041

ABSTRACT

The behavior of matter changes dramatically as the size of the matter decreases?especially when the size decreases to the nanometer regime. These very small pieces of matter are called nanoparticles, and these nanoparticles are useful to people. For example, home pregnancy tests use nanoparticles, Covid-19 vaccines use nanoparticles, and state-of-the-art televisions use nanoparticles. Nanoparticles can also be used to deliver materials (e.g., drugs or genetic material) to cells. One challenge with nanoparticles is that they are often very unstable and clump together, and these clumps of nanoparticles do not have the same properties as individual nanoparticles. Thus, this research will create new ways of controlling how nanoparticles clump together. The research is based on prior work showing that tiny pieces of protein can cause nanoparticles to assemble in a reversible way. Thus, the nano-scale properties of the material can be turned on and off based on the presence of the protein. This research will first study different kinds of protein to determine how the clumping and de-clumping occur. The research will then study different kinds of nanoparticles to understand the range of nanoparticle types that can be used. Activities include both laboratory-based research and computational modeling. A final phase of the research will focus on fungal cells and the interactions of these nanoparticles with fungal cells. Fungi are important because they can cause disease, be consumed as food, or be used for biomanufacturing. The outcome of this research will be new knowledge about how to store and stabilize nanoparticles as well as new knowledge about how to control the properties of fungal cells with nanoparticles.

Nanoparticles are colloidally stable when the repulsive electrostatic and steric forces are balanced by the attractive Van der Waals forces. Prior work showed that a di-arginine peptide could induce reversible nanoparticle aggregation (and thus plasmonic coupling) by modulating these surface forces. This research will derive a coherent mechanistic understanding of how the peptide length, amino acid sequence, and nanoparticle surface impact this reversible aggregation. Objective 1 will study the structure/function relationship of peptide length and charge: The research will monitor nanoparticle aggregation and resuspension via plasmonic coupling including in biological and environmental media (e.g., saliva and seawater). Objective 2 will change the nanoparticle size to confirm the role of Van der Waals forces and optimize the color change during assembly/disassembly. Objectives 1 and 2 will combine computational modeling and laboratory assays. Objective 3 will use these lessons learned to measure the interaction and transport of aggregated and free nanoparticles across fungal cell walls as a function of protease expression. This work will create new knowledge in different domains: 1) how plasmonic materials assemble and disassemble; 2) how to store nanoparticles in a dry and aggregated state; 3) how to redisperse nanoparticles in biological and environmental media; and 4) how aggregated and free nanoparticles interact with fungal cells and fungal proteases. PI Jokerst and Co-I Miller will create ?plasmonic pride flags? via different plasmonic nanoparticles and teach the underlying science to a Hispanic Serving Institution in SanDiego as well as LGBT+ advocacy groups. Through these student groups, the PIs activities will help retain LGBT+ students in STEM. Additional educational objectives include hosting visiting summer students who will learn computational methods with Co-I Pascal.

This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

PUBLICATIONS PRODUCED AS A RESULT OF THIS RESEARCH

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Amer, Lubna and Retout, Maurice and Jokerst, Jesse V "Activatable prodrug for controlled release of an antimicrobial peptide via the proteases overexpressed in Candida albicans and Porphyromonas gingivalis" Theranostics , v.14 , 2024 https://doi.org/10.7150/thno.91165 Citation Details
Jin, Zhicheng and Yim, Wonjun and Retout, Maurice and Housel, Emily and Zhong, Wenbin and Zhou, Jiajing and Strano, Michael S and Jokerst, Jesse V "Colorimetric sensing for translational applications: from colorants to mechanisms" Chemical Society Reviews , v.53 , 2024 https://doi.org/10.1039/D4CS00328D Citation Details

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