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Development of a mechanosensitive synthetic cell for mediating intercellular communication.

开发用于介导细胞间通讯的机械敏感合成细胞。

基本信息

批准号：
10722432
负责人：
Allen Po-Chih Liu
金额：
$ 4.68万
依托单位：
UNIVERSITY OF MICHIGAN AT ANN ARBOR
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-09-02 至 2025-05-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10722432
关键词：
Adhesions Adhesives Apoptosis Behavior Binding Biochemical Biocompatible Materials Biological Markers Biomimetics Blood Platelets Blood Vessels Calcium Calpain Cardiovascular system Cell Death Cell Therapy Cell model Cells Coculture Techniques Communication Complex Coupling Cytoplasmic Granules Data Development Disease Encapsulated Endothelial Cells Engineering Environment Enzymes Epidermal Growth Factor Receptor Exocytosis Extracellular Matrix Fostering Future Goals Growth Health Human body Hybrids Immunotherapy In Vitro Lateral Ligands Lipid Bilayers Liquid substance Location Lytic Mammalian Cell Measures Mechanics Mediating Membrane Membrane Fusion Mission Modeling Monitor Morphology Oxidation-Reduction Pathology Patients Peptides Physiological Polymers Probability Process Proliferating Property Public Health Research Research Personnel Signal Transduction Signal Transduction Pathway Specificity Stimulus Surface System T-Lymphocyte Techniques Testing Therapeutic Tissues United States National Institutes of Health Variant Vascular Endothelial Growth Factors Vesicle Work biological adaptation to stress cancer cell cell killing cell type chimeric antigen receptor density exosome experience hemodynamics improved innovation intercellular communication interest mechanical force mechanotransduction membrane reconstitution novel prevent receptor binding reconstitution response shear stress stem cells success synthetic biology technology platform tool tumor

项目摘要

Project Summary Our abilities to engineer synthetic cell systems that can communicate with living cells remain limited. The long-term goal is to engineer cell-like systems with increasingly complex biomimetic functions that can serve as cell replacement or augment functions of natural cells. The objective of this proposal is to develop a mechanosensitive synthetic cell that can respond to an increase in shear stress, which is most prevalent in the cardiovascular system, and secrete bioactive molecules to effect living cells. Cells in our bodies constantly sense and respond to microenvironmental stimuli, including passive and active physical stimuli, such as extracellular matrix rigidity, adhesive ligand density, tension, compression, and fluid shear flow. The rationale underlying this proposal is that completion will result in a novel biomimetic cell-like system as a novel shear stress-responsive ‘material’ that can interface with natural living cells. The majority of engineered biomaterials respond to differences in the biochemical environment (e.g. differences in redox, pH, and enzyme composition) between normal and diseased tissues. By comparison, there has been relatively less effort in exploiting forces for stimulus-responsive behaviors. The synthetic cell idea is inspired by natural platelets’ ability to bind and respond to elevated shear stress and secrete granule contents when bound to a surface. The proposed work consists of three specific aims: 1) Characterize shear stress response of mechanosensing vesicles, 2) Couple mechanosensing with exocytosis in synthetic cells, 3) Test intercellular communication of shear stress-activated synthetic cells with endothelial cells in vitro. We will pursue these aims using an innovative approach of repurposing mechanosensitive channel for shear stress sensing and using peptide-based membrane fusion. Our lab was the first group to demonstrate mechanosensing synthetic cells and we have significant expertise in bottom-up synthetic biology. The proposed research is significant, because it will be the first synthetic cell system developed to communicate with mammalian cells using calcium-triggered secretion. The work will develop fundamental strategies for coupling mechanosensing to a biochemical response in synthetic cells. This will open new avenue for other researchers interested in developing more complex cell-like systems. The results will have an important positive impact immediately because it will support the idea that mechanosensitive channels can sense lateral membrane tension due to shear stress and long-term because they lay the groundwork of engineering synthetic cells with other sensing abilities.

项目总结

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Membrane stretching activates calcium permeability of a putative channel Pkd2 during fission yeast cytokinesis.

DOI：
10.1091/mbc.e22-07-0248
发表时间：
2022-12-01
期刊：
MOLECULAR BIOLOGY OF THE CELL
影响因子：
3.3
作者：
Poddar, Abhishek;Hsu, Yen-Yu;Zhang, Faith;Shamma, Abeda;Kreais, Zachary;Muller, Clare;Malla, Mamata;Ray, Aniruddha;Liu, Allen P.;Chen, Qian
通讯作者：
Chen, Qian

Hybrid Vesicles Enable Mechano-Responsive Hydrogel Degradation.

混合囊泡可实现机械响应水凝胶降解。

DOI：
10.1002/anie.202308509
发表时间：
2023
期刊：
Angewandte Chemie (International ed. in English)
影响因子：
0
作者：
Hwang,Sung-Won;Lim,Chung-Man;Huynh,CongTruc;Moghimianavval,Hossein;Kotov,NicholasA;Alsberg,Eben;Liu,AllenP
通讯作者：
Liu,AllenP

Methods to mechanically perturb and characterize GUV-based minimal cell models.