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Polish Academy of Sciences

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Carlo Manzo

ICFO, Institut de Ciències Fotòniques (ES)

Recent publications
1.  Piechocka I.K., Keary S., Sosa-Costa A., Lau L., Mohan N., Stanisavljevic J., Borgman K.J.E., Lakadamyali M., Manzo C., Garcia-Parajo M.F., Shear forces induce ICAM-1 nanoclustering on endothelial cells that impact on T-cell migration, BIOPHYSICAL JOURNAL, ISSN: 0006-3495, DOI: 10.1016/j.bpj.2021.05.016, Vol.120, No.13, pp.2644-2656, 2021

Abstract:
The leukocyte-specific β2-integrin LFA-1 and its ligand ICAM-1, expressed on endothelial cells (ECs), are involved in the arrest, adhesion, and transendothelial migration of leukocytes. Although the role of mechanical forces on LFA-1 activation is well established, the impact of forces on its major ligand ICAM-1 has received less attention. Using a parallel-plate flow chamber combined with confocal and super-resolution microscopy, we show that prolonged shear flow induces global translocation of ICAM-1 on ECs upstream of flow direction. Interestingly, shear forces caused actin rearrangements and promoted actin-dependent ICAM-1 nanoclustering before LFA-1 engagement. T cells adhered to mechanically prestimulated ECs or nanoclustered ICAM-1 substrates developed a promigratory phenotype, migrated faster, and exhibited shorter-lived interactions with ECs than when adhered to non mechanically stimulated ECs or to monomeric ICAM-1 substrates. Together, our results indicate that shear forces increase ICAM-1/LFA-1 bonds because of ICAM-1 nanoclustering, strengthening adhesion and allowing cells to exert higher traction forces required for faster migration. Our data also underscore the importance of mechanical forces regulating the nanoscale organization of membrane receptors and their contribution to cell adhesion regulation.

Affiliations:
Piechocka I.K. - IPPT PAN
Keary S. - Barcelona Institute of Science and Technology (ES)
Sosa-Costa A. - Barcelona Institute of Science and Technology (ES)
Lau L. - Barcelona Institute of Science and Technology (ES)
Mohan N. - Barcelona Institute of Science and Technology (ES)
Stanisavljevic J. - Barcelona Institute of Science and Technology (ES)
Borgman K.J.E. - Barcelona Institute of Science and Technology (ES)
Lakadamyali M. - University of Pennsylvania (US)
Manzo C. - ICFO, Institut de Ciències Fotòniques (ES)
Garcia-Parajo M.F. - Barcelona Institute of Science and Technology (ES)
2.  Sosa-Costa A., Piechocka I.K., Gardini L., Pavone F.S., Capitanio M., Garcia-Parajo M.F., Manzo C., PLANT: A Method for Detecting Changes of Slope in Noisy Trajectories, BIOPHYSICAL JOURNAL, ISSN: 0006-3495, DOI: 10.1016/j.bpj.2018.04.006, Vol.114, No.9, pp.2044-2051, 2018

Abstract:
Time traces obtained from a variety of biophysical experiments contain valuable information on underlying processes occurring at the molecular level. Accurate quantification of these data can help explain the details of the complex dynamics of biological systems. Here, we describe PLANT (Piecewise Linear Approximation of Noisy Trajectories), a segmentation algorithm that allows the reconstruction of time-trace data with constant noise as consecutive straight lines, from which changes of slopes and their respective durations can be extracted. We present a general description of the algorithm and perform extensive simulations to characterize its strengths and limitations, providing a rationale for the performance of the algorithm in the different conditions tested. We further apply the algorithm to experimental data obtained from tracking the centroid position of lymphocytes migrating under the effect of a laminar flow and from single myosin molecules interacting with actin in a dual-trap force-clamp configuration.

Keywords:
TETHERED PARTICLE MOTION, CHANGE-POINT DETECTION, OPTICAL TWEEZERS, CELL-ADHESION, UNKNOWN POINT, SINGLE, MYOSIN, MODEL, MIGRATION, TRACKING

Affiliations:
Sosa-Costa A. - Barcelona Institute of Science and Technology (ES)
Piechocka I.K. - IPPT PAN
Gardini L. - National Institute of Optics–National Research Council (IT)
Pavone F.S. - University of Florence (IT)
Capitanio M. - University of Florence (IT)
Garcia-Parajo M.F. - Barcelona Institute of Science and Technology (ES)
Manzo C. - ICFO, Institut de Ciències Fotòniques (ES)

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