DNA probes for monitoring dynamic and transient molecular encounters on live cell membranes.
Cells interact with the extracellular environment through molecules expressed on the membrane. Disruption of these membrane-bound interactions (or encounters) can result in disease progression. Advances in super-resolution microscopy have allowed membrane encounters to be examined, however, these methods cannot image entire membranes and cannot provide information on the dynamic interactions between membrane-bound molecules. Here, we show a novel DNA probe that can transduce transient membrane encounter events into readable cumulative fluorescence signals. The probe, which translocates from one anchor site to another, mimicking motor proteins, is realized through a toehold-mediated DNA strand displacement reaction. Using this probe, we successfully monitored rapid encounter events of membrane lipid domains using flow cytometry and fluorescence microscopy. Our results show a preference for encounters within the same lipid domains.
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, People's Republic of China.|Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.|Department of Chemistry, University of Massachusetts Amherst, Amherst, Massachusetts 01003, USA.|Department of Mathematics, Michigan State University, East Lansing, Michigan 48824, USA.
Mingxu
M
You
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, People's Republic of China.|Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.
Yifan
Y
Lyu
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, People's Republic of China.|Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.
Da
D
Han
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, People's Republic of China.|Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.
Liping
L
Qiu
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, People's Republic of China.
Qiaoling
Q
Liu
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, People's Republic of China.|Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.
Tao
T
Chen
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, People's Republic of China.|Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.
Cuichen
C
Sam Wu
Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.
Lu
L
Peng
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, People's Republic of China.|Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.
Liqin
0000-0002-3632-4117
L
Zhang
School of Mathematical Sciences, Zhejiang University, Hangzhou, Zhejiang 310027, People's Republic of China.
Gang
G
Bao
Molecular Science and Biomedicine Laboratory, State Key Laboratory of Chemo/Bio-sensing and Chemometrics, College of Chemistry and Chemical Engineering, College of Biology, Collaborative Innovation Center for Chemistry and Molecular Medicine, Hunan University, Changsha 410082, People's Republic of China.|Department of Chemistry and Department of Physiology and Functional Genomics, Center for Research at the Bio/Nano Interface, Health Cancer Center, UF Genetics Institute, McKnight Brain Institute, University of Florida, Gainesville, Florida 32611, USA.
Weihong
W
Tan
D000818:Animals; D001693:Biological Transport, Active / Q000502:physiology; D002417:Cattle; D002460:Cell Line; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D015342:DNA Probes / Q000737:chemistry* / Q000494:pharmacology*; D008856:Microscopy, Fluorescence; D057054:Molecular Imaging; D012710:Serum Albumin, Bovine
D015342:DNA Probes; D012710:Serum Albumin, Bovine