Information updated Jan 2025
Visualise integrin αIIbβ3 dynamics and its interactome in platelet clotting
By working very closely with Prof Arnold JU from the School of Biomedical Engineering and the Heart Research Institute (HRI) at the University of Sydney (USYD), I have established the TIRF/HiLoM/ STORM systems at UTS and USYD, for human blood clotting platelet. With a palette of new organic probes and dye-conjugated antibodies, we have mapped the spatio-temporal distribution of integrin αIIbβ3 with “bent” vs. “extended” conformation attributed to “resting” vs. “activated” platelets respectively at single-cell and single-molecule level. Furthermore, I performed multi-colour single-molecule tracking to correlate these integrin conformation states with the dynamics of the cell membrane, actin, and microtubules. This interactome analysis demonstrates that the resting integrin distribute ahead of membrane spreading followed by the activated integrin in sequence, suggesting the role of integrin activation in leading the molecular machinery during the platelet spreading and aggregation process.
My further STORM analysis further mapped integrin αIIbβ3 conformational landscape across different stages of platelet activation at single-molecule resolution (~20 nm). The molecular “fingerprints” obtained by my SM/SR imaging approaches will conceptually advance the knowledge on integrin structure, affinity regulation and dynamics which sheds light to novel integrin targeting therapeutics in future.
[16] Chen Y., L.A. Ju, F. Zhou, J. Liao, L. Xue, Qian Peter Su, D. Jin, Y. Yuan, H. Lu, S.P. Jackson#, C. Zhu#. 2019. An integrin αIIbβ3 intermediate affinity state mediates biomechanical platelet aggregation. Nature Materials DOI: 10.1038/s41563-019-0323-6
[17] Chen C.*, F. Wang*#, S. Wen, Qian Peter Su, M.C.L. Wu, Y. Liu, B. Wang, D. Li, X. Shan, M. Kianinia, I. Aharonovich, M. Toth, S.P. Jackson, P. Xi, D. Jin#. 2018. Multi-photon near-infrared emission saturation nanoscopy using UCNPs. Nature Communications 9, 3290. DOI: 10.1038/s41467-018-05842-w
[18] Su Qian Peter*#(equal contribution, corresponding author) and Lining Arnold Ju*#. 2018. Biophysical Nanotools for Single Molecule Dynamics. Biophysical Reviews 1-9 DOI: 10.1007/s12551-018-0447-y
My further STORM analysis further mapped integrin αIIbβ3 conformational landscape across different stages of platelet activation at single-molecule resolution (~20 nm). The molecular “fingerprints” obtained by my SM/SR imaging approaches will conceptually advance the knowledge on integrin structure, affinity regulation and dynamics which sheds light to novel integrin targeting therapeutics in future.
[16] Chen Y., L.A. Ju, F. Zhou, J. Liao, L. Xue, Qian Peter Su, D. Jin, Y. Yuan, H. Lu, S.P. Jackson#, C. Zhu#. 2019. An integrin αIIbβ3 intermediate affinity state mediates biomechanical platelet aggregation. Nature Materials DOI: 10.1038/s41563-019-0323-6
[17] Chen C.*, F. Wang*#, S. Wen, Qian Peter Su, M.C.L. Wu, Y. Liu, B. Wang, D. Li, X. Shan, M. Kianinia, I. Aharonovich, M. Toth, S.P. Jackson, P. Xi, D. Jin#. 2018. Multi-photon near-infrared emission saturation nanoscopy using UCNPs. Nature Communications 9, 3290. DOI: 10.1038/s41467-018-05842-w
[18] Su Qian Peter*#(equal contribution, corresponding author) and Lining Arnold Ju*#. 2018. Biophysical Nanotools for Single Molecule Dynamics. Biophysical Reviews 1-9 DOI: 10.1007/s12551-018-0447-y
|
|
|
|
Funding Bodies
|
|
|
|
|
NHMRC Investigator Grant - Emerging Leadership 1
Heart Foundation PostDoc Fellowship
ARC Discovery Project
UTS Funding
Heart Foundation PostDoc Fellowship
ARC Discovery Project
UTS Funding