Engineering in-cellulo mesoporous protein crystals as genetically programmable functional biomaterials
Abstract
Building nanostructures with self-assembled biomolecules has held great promise to recapitulate nature s elegance and create nanostructures with on-demand characteristics. Nevertheless, current protein nanostructures primarily assemble in vitro with concentrated building blocks and thus involve laborious processes, restricted assembly conditions, and modest structural stability. The discovery of in-cellulo protein crystals, those nucleate and grow in live cells, suggests an exciting synthetic pathway toward functional protein nanostructures that circumvent the limitations of in-vitro assembly. In addition, in-cellulo protein crystallization offers the unique capability to program the materials synthesis in real-time via the control of the intracellular protein interactions and regulatory networks. Although the in-cellulo crystals exhibit unique properties and programmability, few studies, if any, have synthesized and programed them into functional materials. Therefore, we propose to fill the knowledge and technological gaps by thoroughly characterizing the in-cellulo crystals, engineering new variants of the building blocks to tune the crystal growth and surface chemistry, and eventually delivering synthetic strategies that endow the protein nanomaterials with structural, chemical, and biochemical programmability. We will attain the goals via three specific aims. In Aim 1, we will exploit fluorescence imaging and advanced materials characterization to study the growth kinetics, stability, and mechanical properties of representative in-cellulo crystals. In Aim 2, we will engineer the building blocks of in-cellulo crystals to alter crystal growth and surface chemistry. In Aim 3, We will exploit inducible mediation of intracellular processes to control the growth in-cellulo crystals, and eventually obtain in-cellulo crystals that can be programmed with nanoscale precision. We believe the in-cellulo protein crystals will emerge as a new class of functional natural materials with programmability that is hitherto challenging in materials synthesis.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Feb 29, 2024
- Source ID
- FA95502310174
Entities
People
- Dingchang Lin
Organizations
- Air Force Office of Scientific Research
- Johns Hopkins University
- United States Air Force