Active Probes for Imaging Membrane Dynamics of Live Cells with High Spatial and Temporal Resolution over Extended Time Scales and Areas

Overview

Journal J Am Chem Soc

Publisher American Chemical Society

Specialty Chemistry

Date 2018 Feb 27

PMID 29481071

Citations 26

Authors

Huaimin Wang

Zhaoqianqi Feng

Steven J Del Signore

Avital A Rodal

Bing Xu

Affiliations

Soon will be listed here.

Abstract

Despite the advancement of molecular imaging techniques, there is an unmet need for probes for direct imaging of membrane dynamics of live cells. Here we report a novel type of active (or enzyme responsive) probes to directly image membrane dynamics of live cells with high spatial and temporal resolution over extended time scales and areas. Because lipid rafts enrich cholesterols and GPI-anchored enzymes (e.g., ectophosphatases), we design probes that consist of an enzymatic trigger, a fluorophore, and a cholesterol that are affinitive to the cell membrane. Being water-soluble and as the substrate of ectophosphatase, these cell compatible probes preferentially and rapidly assemble in plasma membrane, exhibit strong fluorescence, work at micromolar concentrations, and easily achieve high resolution monitoring of nanoscale heterogeneity in membranes of live cells, the release of exosomes, and the membrane dynamics of live cells. This work provides a facile means to link membrane dynamics and heterogeneity to cellular processes for understanding the interactions between membranes and proteins.

Citing Articles

Design strategies for organelle-selective fluorescent probes: where to start?.

Alamudi S, Lee Y RSC Adv. 2025; 15(3):2115-2131.

PMID: 39845114 PMC: 11752733. DOI: 10.1039/d4ra08032g.

Organelle-Specific Smart Supramolecular Materials for Bioimaging and Theranostics Application.

Bharathidasan D, Maity C Top Curr Chem (Cham). 2024; 383(1):1.

PMID: 39607460 DOI: 10.1007/s41061-024-00483-8.

Mechanical activation of TWIK-related potassium channel by nanoscopic movement and rapid second messenger signaling.

Petersen E, Pavel M, Hansen S, Gudheti M, Wang H, Yuan Z Elife. 2024; 12.

PMID: 38407149 PMC: 10942622. DOI: 10.7554/eLife.89465.

Enzyme-Directed and Organelle-Specific Sphere-to-Fiber Nanotransformation Enhances Photodynamic Therapy in Cancer Cells.

Gan S, Yang L, Heng Y, Chen Q, Wang D, Zhang J Small Methods. 2024; 8(11):e2301551.

PMID: 38369941 PMC: 11579569. DOI: 10.1002/smtd.202301551.

Peptide Supramolecular Assembly-Instructed In Situ Self-Aggregation for Stratified Targeting Sonodynamic Therapy Enhancement of AIE Luminogens.

Jiang W, Cheng C, Qiu X, Chen L, Guo X, Luo Y Adv Sci (Weinh). 2022; 10(4):e2204989.

PMID: 36494092 PMC: 9896067. DOI: 10.1002/advs.202204989.

References

Feng Z, Zhang T, Wang H, Xu B . Supramolecular catalysis and dynamic assemblies for medicine. Chem Soc Rev. 2017; 46(21):6470-6479. PMC: 5662491. DOI: 10.1039/c7cs00472a. View

Liang Y, Lynn D, Berland K . Direct observation of nucleation and growth in amyloid self-assembly. J Am Chem Soc. 2010; 132(18):6306-8. DOI: 10.1021/ja910964c. View

Gao Y, Shi J, Yuan D, Xu B . Imaging enzyme-triggered self-assembly of small molecules inside live cells. Nat Commun. 2012; 3:1033. PMC: 3521559. DOI: 10.1038/ncomms2040. View

Schoneberg J, Lehmann M, Ullrich A, Posor Y, Lo W, Lichtner G . Lipid-mediated PX-BAR domain recruitment couples local membrane constriction to endocytic vesicle fission. Nat Commun. 2017; 8:15873. PMC: 5481832. DOI: 10.1038/ncomms15873. View

Liang C, Ni R, Smith J, Childers W, Mehta A, Lynn D . Kinetic intermediates in amyloid assembly. J Am Chem Soc. 2014; 136(43):15146-9. DOI: 10.1021/ja508621b. View

Simons K, Ikonen E . How cells handle cholesterol. Science. 2000; 290(5497):1721-6. DOI: 10.1126/science.290.5497.1721. View

Paolo G, De Camilli P . Phosphoinositides in cell regulation and membrane dynamics. Nature. 2006; 443(7112):651-7. DOI: 10.1038/nature05185. View

Feng Z, Wang H, Chen X, Xu B . Self-Assembling Ability Determines the Activity of Enzyme-Instructed Self-Assembly for Inhibiting Cancer Cells. J Am Chem Soc. 2017; 139(43):15377-15384. PMC: 5669277. DOI: 10.1021/jacs.7b07147. View

Moon S, Yan R, Kenny S, Shyu Y, Xiang L, Li W . Spectrally Resolved, Functional Super-Resolution Microscopy Reveals Nanoscale Compositional Heterogeneity in Live-Cell Membranes. J Am Chem Soc. 2017; 139(32):10944-10947. DOI: 10.1021/jacs.7b03846. View

10.

Scita G, Di Fiore P . The endocytic matrix. Nature. 2010; 463(7280):464-73. DOI: 10.1038/nature08910. View

11.

Debnath S, Roy S, Ulijn R . Peptide nanofibers with dynamic instability through nonequilibrium biocatalytic assembly. J Am Chem Soc. 2013; 135(45):16789-92. DOI: 10.1021/ja4086353. View

12.

Gao W, Xing B, Tsien R, Rao J . Novel fluorogenic substrates for imaging beta-lactamase gene expression. J Am Chem Soc. 2005; 125(37):11146-7. DOI: 10.1021/ja036126o. View

13.

Dahl R, Sergienko E, Su Y, Mostofi Y, Yang L, Simao A . Discovery and validation of a series of aryl sulfonamides as selective inhibitors of tissue-nonspecific alkaline phosphatase (TNAP). J Med Chem. 2009; 52(21):6919-25. PMC: 2783186. DOI: 10.1021/jm900383s. View

14.

CARY L, Cooper J . Molecular switches in lipid rafts. Nature. 2000; 404(6781):945, 947. DOI: 10.1038/35010257. View

15.

Komura N, Suzuki K, Ando H, Konishi M, Koikeda M, Imamura A . Raft-based interactions of gangliosides with a GPI-anchored receptor. Nat Chem Biol. 2016; 12(6):402-10. DOI: 10.1038/nchembio.2059. View

16.

Baumgart T, Hunt G, Farkas E, Webb W, Feigenson G . Fluorescence probe partitioning between Lo/Ld phases in lipid membranes. Biochim Biophys Acta. 2007; 1768(9):2182-94. PMC: 2702987. DOI: 10.1016/j.bbamem.2007.05.012. View

17.

Takaoka Y, Sakamoto T, Tsukiji S, Narazaki M, Matsuda T, Tochio H . Self-assembling nanoprobes that display off/on 19F nuclear magnetic resonance signals for protein detection and imaging. Nat Chem. 2011; 1(7):557-61. DOI: 10.1038/nchem.365. View

18.

van den Bogaart G, Meyenberg K, Risselada H, Amin H, Willig K, Hubrich B . Membrane protein sequestering by ionic protein-lipid interactions. Nature. 2011; 479(7374):552-5. PMC: 3409895. DOI: 10.1038/nature10545. View

19.

Morris D, Masuhara K, Takaoka K, Ono K, Anderson H . Immunolocalization of alkaline phosphatase in osteoblasts and matrix vesicles of human fetal bone. Bone Miner. 1992; 19(3):287-98. DOI: 10.1016/0169-6009(92)90877-g. View

20.

Feng Z, Wang H, Zhou R, Li J, Xu B . Enzyme-Instructed Assembly and Disassembly Processes for Targeting Downregulation in Cancer Cells. J Am Chem Soc. 2017; 139(11):3950-3953. PMC: 5380121. DOI: 10.1021/jacs.7b00070. View