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LINC complex-Lis1 interplay controls MT1-MMP matrix digest-on-demand response for confined tumor cell migration.
Elvira Infante, Alessia Castagnino, Robin Ferrari, Pedro Monteiro, Sonia Agüera-González, Perrine Paul-Gilloteaux, Mélanie J Domingues, Paolo Maiuri, Matthew Raab, Catherine M Shanahan, Alexandre Baffet, Matthieu Piel, Edgar R Gomes, Philippe Chavrier
Nature Communications - 9 2443 - DOI : 10.1038/s41467-018-04865-7 - 2018
Cancer cells’ ability to migrate through constricting pores in the tissue matrix is limited by nuclear stiffness. MT1-MMP contributes to metastasis by widening matrix pores, facilitating confined migration. Here, we show that modulation of matrix pore size or of lamin A expression known to modulate nuclear stiffness directly impinges on levels of MT1-MMP-mediated pericellular collagenolysis by cancer cells. A component of this adaptive response is the centrosome-centered distribution of MT1-MMP intracellular storage compartments ahead of the nucleus. We further show that this response, including invadopodia formation in association with confining matrix fibrils, requires an intact connection between the nucleus and the centrosome via the linker of nucleoskeleton and cytoskeleton (LINC) complex protein nesprin-2 and dynein adaptor Lis1. Our results uncover a digest-on-demand strategy for nuclear translocation through constricted spaces whereby confined migration triggers polarization of MT1-MMP storage compartments and matrix proteolysis in front of the nucleus depending on nucleus-microtubule linkage.
Role of calcium permeable channels in dendritic cell migration.
Sáez PJ, Sáez JC, Lennon-Duménil AM, Vargas P.
Curr Opin Immunol. - 52 74-80 - doi: 10.1016/j.coi.2018.04 - 2018
Calcium ion (Ca2+) is an essential second messenger involved in multiple cellular and subcellular processes. Ca2+ can be released and sensed globally or locally within cells, providing complex signals of variable amplitudes and time-scales. The key function of Ca2+ in the regulation of acto-myosin contractility has provided a simple explanation for its role in the regulation of immune cell migration. However, many questions remain, including the identity of the Ca2+ stores, channels and upstream signals involved in this process. Here, we focus on dendritic cells (DCs), because their immune sentinel function heavily relies on their capacity to migrate within tissues and later on between tissues and lymphoid organs. Deciphering the mechanisms by which cytoplasmic Ca2+ regulate DC migration should shed light on their role in initiating and tuning immune responses.
Mixed Copolymer Adlayers Allowing Reversible Thermal Control of Single Cell Aspect Ratio.
Dalier F, Dubacheva GV, Coniel M, Zanchi D, Galtayries A, Piel M, Marie E, Tribet C.
ACS Appl Mater Interfaces - 10(3) 2253-2258 - doi: 10.1021/acsami.7b18513. - 2018
Dynamic guidance of living cells is achieved by fine-tuning and spatiotemporal modulation on artificial polymer layers enabling reversible peptide display. Adjustment of surface composition and interactions is obtained by coadsorption of mixed poly(lysine) derivatives, grafted with either repellent PEG, RGD adhesion peptides, or T-responsive poly(N-isopropylacrylamide) strands. Deposition of mixed adlayers provides a straightforward mean to optimize complex substrates, which is here implemented to achieve (1) thermal control of ligand accessibility and (2) adjustment of relative adhesiveness between adjacent micropatterns, while preserving cell attachment during thermal cycles. The reversible polarization of HeLa cells along orthogonal stripes mimics guidance along natural matrices.
Retraction Notice to: FMN2 Makes Perinuclear Actin to Protect Nuclei during Confined Migration and Promote Metastasis.
Skau CT, Fischer RS, Gurel P, Thiam HR, Tubbs A, Baird MA, Davidson MW, Piel M, Alushin GM, Nussenzweig A, Steeg PS, Waterman CM.
Cell - 173(2) 529 - doi: 10.1016/j.cell.2018.03.058 - 2018
FMN2 Makes Perinuclear Actin to Protect Nuclei during Confined Migration and Promote Metastasis. [Cell. 2016]
Leukocyte Migration and Deformation in Collagen Gels and Microfabricated Constrictions
Sáez PJ, Barbier L, Attia R, Thiam HR, Piel M, Vargas P.
Methods Mol Biol. - 1749 361-373 - doi: 10.1007/978-1-4939-7701-7_26. - 2018
In multicellular organisms, cell migration is a complex process. Examples of this are observed during cell motility in the interstitial space, full of extracellular matrix fibers, or when cells pass through endothelial layers to colonize or exit specific tissues. A common parameter for both situations is the fast adaptation of the cellular shape to their irregular landscape. In this chapter, we describe two methods to study cell migration in complex environments. The first one consists in a multichamber device for the visualization of cell haptotaxis toward the collagen-binding chemokine CCL21. This method is used to study cell migration as well as deformations during directed motility, as in the interstitial space. The second one consists in microfabricated channels connected to small constrictions. This procedure allows the study of cell deformations when single cells migrate through small holes and it is analogous to passage of cells through endothelial layers, resulting in a simplified system to study the mechanisms operating during transvasation. Both methods combined provide a powerful hub for the study of cell plasticity during migration in complex environments.
Leukocyte Migration and Deformation in Collagen Gels and Microfabricated Constrictions.
Sáez PJ, Barbier L, Attia R, Thiam HR, Piel M, Vargas P
Methods Mol Biol. - 1749 361-373 - doi: 10.1007/978-1-4939-7701-7_26 - 2018
In multicellular organisms, cell migration is a complex process. Examples of this are observed during cell motility in the interstitial space, full of extracellular matrix fibers, or when cells pass through endothelial layers to colonize or exit specific tissues. A common parameter for both situations is the fast adaptation of the cellular shape to their irregular landscape. In this chapter, we describe two methods to study cell migration in complex environments. The first one consists in a multichamber device for the visualization of cell haptotaxis toward the collagen-binding chemokine CCL21. This method is used to study cell migration as well as deformations during directed motility, as in the interstitial space. The second one consists in microfabricated channels connected to small constrictions. This procedure allows the study of cell deformations when single cells migrate through small holes and it is analogous to passage of cells through endothelial layers, resulting in a simplified system to study the mechanisms operating during transvasation. Both methods combined provide a powerful hub for the study of cell plasticity during migration in complex environments.
Mixed Copolymer Adlayers Allowing Reversible Thermal Control of Single Cell Aspect Ratio.
Dalier F1, Dubacheva GV1, Coniel M1, Zanchi D1,2, Galtayries A, Piel M, Marie E1, Tribet C1.
ACS Appl Mater Interfaces - 10(3) 2253-2258 - doi: 10.1021/acsami.7b18513. - 2018
Dynamic guidance of living cells is achieved by fine-tuning and spatiotemporal modulation on artificial polymer layers enabling reversible peptide display. Adjustment of surface composition and interactions is obtained by coadsorption of mixed poly(lysine) derivatives, grafted with either repellent PEG, RGD adhesion peptides, or T-responsive poly(N-isopropylacrylamide) strands. Deposition of mixed adlayers provides a straightforward mean to optimize complex substrates, which is here implemented to achieve (1) thermal control of ligand accessibility and (2) adjustment of relative adhesiveness between adjacent micropatterns, while preserving cell attachment during thermal cycles. The reversible polarization of HeLa cells along orthogonal stripes mimics guidance along natural matrices.
Diversification of human plasmacytoid predendritic cells in response to a single stimulus
Alculumbre SG, Saint-André V, Di Domizio J, Vargas P, Sirven P, Bost P, Maurin M, Maiuri P, Wery M, Roman MS, Savey L, Touzot M, Terrier B, Saadoun D, Conrad C, Gilliet M, Morillon A, Soumelis V
Nat Immunol. - 19(1) 63-75 - doi: 10.1038/s41590-017-0012-z. - 2018
Innate immune cells adjust to microbial and inflammatory stimuli through a process termed environmental plasticity, which links a given individual stimulus to a unique activated state. Here, we report that activation of human plasmacytoid predendritic cells (pDCs) with a single microbial or cytokine stimulus triggers cell diversification into three stable subpopulations (P1-P3). P1-pDCs (PD-L1+CD80-) displayed a plasmacytoid morphology and specialization for type I interferon production. P3-pDCs (PD-L1-CD80+) adopted a dendritic morphology and adaptive immune functions. P2-pDCs (PD-L1+CD80+) displayed both innate and adaptive functions. Each subpopulation expressed a specific coding- and long-noncoding-RNA signature and was stable after secondary stimulation. P1-pDCs were detected in samples from patients with lupus or psoriasis. pDC diversification was independent of cell divisions or preexisting heterogeneity within steady-state pDCs but was controlled by a TNF autocrine and/or paracrine communication loop. Our findings reveal a novel mechanism for diversity and division of labor in innate immune cells.
In situ targeted activation of an anticancer agent using ultrasound-triggered release of composite droplets
Bezagu M, Clarhaut J, Renoux B, Monti F, Tanter M, Tabeling P6, Cossy J, Couture O, Papot S, Arseniyadis S
- 142 44014 - DOI: 10.1016/j.ejmech.2017.03.057 - 2017
The efficiency of a drug is usually highly dependent on the way it is administered or delivered. As such, targeted-therapy, which requires conceiving drug-delivery vehicles that will change their state from a relatively stable structure with a very slow leak-rate to an unstable structure with a fast release, clearly improves the pharmacokinetics, the absorption, the distribution, the metabolism and the therapeutic index of a given drug. In this context, we have developed a particularly effective double stimuli-responsive drug-delivery method allowing an ultrasound-induced release of a monomethylauristatin E-glucuronide prodrug and its subsequent activation by a β-glucuronidase. This led to an increase of cytotoxicity of about 80% on cancer cells.
Study of the Stability and Hydrophilicity of Plasma‐Modified Microfluidic Materials
Bradley Da Silva Mengxue Zhang Guillaume Schelcher Lea Winter Cédric Guyon Patrick Tabeling Daniel Bonn Michael Tatoulian
- - doi.org/10.1002/ppap.201600034 - 2017
Polymers among new classes of materials such as polydimethylsiloxane (PDMS), cyclic olefin copolymer (COC), Norland optical adhesive (NOA), and THV (fluoropolymer) were evaluated as surface‐modified microfluidic materials, including investigating the incorporation of silica‐like functional groups onto these surfaces. The functionalization of these materials was performed using a hybrid reactor equipped with magnetron sputtering using a silica target and with a PECVD apparatus starting from hexamethyldisiloxane as a chemical precursor. Coated microfluidic materials were then evaluated in terms of wettability, stability, composition, and structure. The deposited coatings were proved to be stable up to 2 month in air and water storage for these materials, with COC providing the

410 publications.