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Publications

by Keyword: Motility

Wang, ZH, Klingner, A, Magdanz, V, Hoppenreijs, MW, Misra, S, Khalil, ISM, (2022). Flagellar Propulsion of Sperm Cells Against a Time-Periodic Interaction Force Advanced Biology , 2200210

Sperm cells undergo complex interactions with external environments, such as a solid-boundary, fluid flow, as well as other cells before arriving at the fertilization site. The interaction with the oviductal epithelium, as a site of sperm storage, is one type of cell-to-cell interaction that serves as a selection mechanism. Abnormal sperm cells with poor swimming performance, the major cause of male infertility, are filtered out by this selection mechanism. In this study, collinear bundles, consisting of two sperm cells, generate propulsive thrusts along opposite directions and allow to observe the influence of cell-to-cell interaction on flagellar wave-patterns. The developed elasto-hydrodynamic model demonstrates that steric and adhesive forces lead to highly symmetrical wave-pattern and reduce the bending amplitude of the propagating wave. It is measured that the free cells exhibit a mean flagellar curvature of 6.4 +/- 3.5 rad mm(-1) and a bending amplitude of 13.8 +/- 2.8 rad mm(-1). After forming the collinear bundle, the mean flagellar curvature and bending amplitude are decreased to 1.8 +/- 1.1 and 9.6 +/- 1.4 rad mm(-1), respectively. This study presents consistent theoretical and experimental results important for understanding the adaptive behavior of sperm cells to the external time-periodic force encountered during sperm-egg interaction.

JTD Keywords: Bovine sperm cells, Cell-to-cell interaction, Cilia, Filaments, Flagellar propulsion, Hydrodynamic models, Mechanism, Micro-video, Model, Motility, Thermotaxis, Transformations, Transition


Joseph A, Wagner AM, Garay-Sarmiento M, Aleksanyan M, Haraszti T, Söder D, Georgiev VN, Dimova R, Percec V, Rodriguez-Emmenegger C, (2022). Zwitterionic Dendrimersomes: A Closer Xenobiotic Mimic of Cell Membranes Advanced Materials , e2206288

Building functional mimics of cell membranes is an important task toward the development of synthetic cells. So far, lipid and amphiphilic block copolymers are the most widely used amphiphiles with the bilayers by the former lacking stability while membranes by the latter are typically characterized by very slow dynamics. Herein, we introduce a new type of Janus dendrimer containing a zwitterionic phosphocholine hydrophilic headgroup (JDPC ) and a 3,5-substituted dihydrobenzoate-based hydrophobic dendron. JDPC self-assembles in water into zwitterionic dendrimersomes (z-DSs) that faithfully recapitulate the cell membrane in thickness, flexibility, and fluidity, while being resilient to harsh conditions and displaying faster pore closing dynamics in the event of membrane rupture. This enables the fabrication of hybrid DSs with components of natural membranes, including pore-forming peptides, structure-directing lipids, and glycans to create raft-like domains or onion vesicles. Moreover, z-DSs can be used to create active synthetic cells with life-like features that mimic vesicle fusion and motility as well as environmental sensing. Despite their fully synthetic nature, z-DSs are minimal cell mimics that can integrate and interact with living matter with the programmability to imitate life-like features and beyond. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.

JTD Keywords: Biosensor, Bottom-up synthetic biology, Hybrid vesicles, Synthetic cells, Vesicle fusion, Vesicle motility, Zwitterionic dendrimersomes


Chattopadhyay, P, Magdanz, V, Hernandez-Melia, M, Borchert, KBL, Schwarz, D, Simmchen, J, (2022). Size-Dependent Inhibition of Sperm Motility by Copper Particles as a Path toward Male Contraception Advanced Nanobiomed Research 2, 2100152

Effective inhibition of sperm motility using a spermicide can be a promising approach in developing non-invasive male contraceptive agents. Copper is known to have contraceptive properties and has been used clinically for decades as intrauterine contraceptive devices (IUDs) for contraception in females. Beyond that, the spermicidal use of copper is not explored much further, even though its use can also subdue the harmful effects caused by the hormonal female contraceptive agents on the environment. Herein, the size, concentration, and time-dependent in vitro inhibition of bovine spermatozoa by copper microparticles are studied. The effectivity in inhibiting sperm motility is correlated with the amount of Cu2+ ions released by the particles during incubation. The copper particles cause direct suppression of sperm motility and viability upon incubation and thereby show potential as sperm-inhibiting, hormone-free candidate for male contraception. In addition, biocompatibility tests using a cervical cell line help optimizing the size and concentration of the copper particles for the best spermicidal action while avoiding toxicity to the surrounding tissue.

JTD Keywords: Bovine spermatozoa, Clinical-trial, Copper, Human-spermatozoa, Ions, Male contraception, Metallic copper, Microparticles, Progestins, Sperm motility, Sperm viability, Spermicide, Viability


Clark, AG, Maitra, A, Jacques, C, Bergert, M, Perez-Gonzalez, C, Simon, A, Lederer, L, Diz-Munoz, A, Trepat, X, Voituriez, R, Vignjevic, DM, (2022). Self-generated gradients steer collective migration on viscoelastic collagen networks Nature Materials 21, 1200-1210

Growing evidence suggests that the physical properties of the cellular microenvironment influence cell migration. However, it is not currently understood how active physical remodelling by cells affects migration dynamics. Here we report that cell clusters seeded on deformable collagen-I networks display persistent collective migration despite not showing any apparent intrinsic polarity. Clusters generate transient gradients in collagen density and alignment due to viscoelastic relaxation of the collagen networks. Combining theory and experiments, we show that crosslinking collagen networks or reducing cell cluster size results in reduced network deformation, shorter viscoelastic relaxation time and smaller gradients, leading to lower migration persistence. Traction force and Brillouin microscopy reveal asymmetries in force distributions and collagen stiffness during migration, providing evidence of mechanical cross-talk between cells and their substrate during migration. This physical model provides a mechanism for self-generated directional migration on viscoelastic substrates in the absence of internal biochemical polarity cues.; Cell clusters mechanically reorganize viscoelastic collagen networks, resulting in transient gradients in collagen density, alignment and stiffness that promote spontaneous persistent migration.

JTD Keywords: Cell-migration, Design, Invasion, Limits, Mechanics, Microscopy, Morphogenesis, Motility, Rear, Rigidity


Chen, Tianchi, Callan-Jones, Andrew, Fedorov, Eduard, Ravasio, Andrea, Brugués, Agustí, Ong, Hui Ting, Toyama, Yusuke, Low, Boon Chuan, Trepat, Xavier, Shemesh, Tom, Voituriez, Raphaël, Ladoux, Benoît, (2019). Large-scale curvature sensing by directional actin flow drives cellular migration mode switching Nature Physics 15, (4), 393-402

Cell migration over heterogeneous substrates during wound healing or morphogenetic processes leads to shape changes driven by different organizations of the actin cytoskeleton and by functional changes including lamellipodial protrusions and contractile actin cables. Cells distinguish between cell-sized positive and negative curvatures in their physical environment by forming protrusions at positive curvatures and actin cables at negative curvatures; however, the cellular mechanisms remain unclear. Here, we report that concave edges promote polarized actin structures with actin flow directed towards the cell edge, in contrast to well-documented retrograde flow at convex edges. Anterograde flow and contractility induce a tension anisotropy gradient. A polarized actin network is formed, accompanied by a local polymerization–depolymerization gradient, together with leading-edge contractile actin cables in the front. These cables extend onto non-adherent regions while still maintaining contact with the substrate through focal adhesions. The contraction and dynamic reorganization of this actin structure allows forward movements enabling cell migration over non-adherent regions on the substrate. These versatile functional structures may help cells sense and navigate their environment by adapting to external geometric and mechanical cues.

JTD Keywords: Biopolymers in vivo, Cellular motility


Campillo, N., Falcones, B., Otero, J., Colina, R., Gozal, D., Navajas, D., Farré, R., Almendros, I., (2019). Differential oxygenation in tumor microenvironment modulates macrophage and cancer cell crosstalk: Novel experimental settingand proof of concept Frontiers in Oncology 9, 43

Hypoxia is a common characteristic of many solid tumors that has been associated with tumor aggressiveness. Limited diffusion of oxygen generates a gradient of oxygen availability from the blood vessel to the interstitial space and may underlie the recruitment of macrophages fostering cancer progression. However, the available data based on the recruitment of circulating cells to the tumor microenvironment has been so far carried out by conventional co-culture systems which ignore the hypoxic gradient between the vessel to the tumor interstitium. Here, we have designed a novel easy-to-build cell culture device that enables evaluation of cellular cross-talk and cell migration while they are being simultaneously exposed to different oxygenation environments. As a proof-of-concept of the potential role of differential oxygenation among interacting cells we have evaluated the activation and recruitment of macrophages in response to hypoxic melanoma, breast, and kidney cancer cells. We found that hypoxic melanoma and breast cancer cells co-cultured with normoxic macrophages enhanced their directional migration. By contrast, hypoxic kidney cells were not able to increase their recruitment. We also identified well-described hypoxia-induced pathways which could contribute in the immune cell recruitment (VEGFA and PTGS2 genes). Moreover, melanoma and breast cancer increased their proliferation. However, oxygenation levels affected neither kidney cancer cell proliferation nor gene expression, which in turn resulted in no significant changes in macrophage migration and polarization. Therefore, the cell culture device presented here provides an excellent opportunity for researchers to reproduce the in vivo hypoxic gradients in solid tumors and to study their role in recruiting circulating cells to the tumor in specific types of cancer.

JTD Keywords: Hypoxia gradient, Macrophage motility, Models of host-tumor interactions, Novel assay technology, Tumor progression


Rodriguez-Franco, P., Brugués, A., Marin-Llaurado, A., Conte, V., Solanas, G., Batlle, E., Fredberg, J. J., Roca-Cusachs, P., Sunyer, R., Trepat, X., (2017). Long-lived force patterns and deformation waves at repulsive epithelial boundaries Nature Materials 16, (10), 1029-1036

For an organism to develop and maintain homeostasis, cell types with distinct functions must often be separated by physical boundaries. The formation and maintenance of such boundaries are commonly attributed to mechanisms restricted to the cells lining the boundary. Here we show that, besides these local subcellular mechanisms, the formation and maintenance of tissue boundaries involves long-lived, long-ranged mechanical events. Following contact between two epithelial monolayers expressing, respectively, EphB2 and its ligand ephrinB1, both monolayers exhibit oscillatory patterns of traction forces and intercellular stresses that tend to pull cell-matrix adhesions away from the boundary. With time, monolayers jam, accompanied by the emergence of deformation waves that propagate away from the boundary. This phenomenon is not specific to EphB2/ephrinB1 repulsion but is also present during the formation of boundaries with an inert interface and during fusion of homotypic epithelial layers. Our findings thus unveil a global physical mechanism that sustains tissue separation independently of the biochemical and mechanical features of the local tissue boundary.

JTD Keywords: Biological physics, Cellular motility


Solórzano, Carla, Srikumar, Shabarinath, Canals, Rocío, Juárez, Antonio, Paytubi, Sonia, Madrid, Cristina, (2015). Hha has a defined regulatory role that is not dependent upon H-NS or StpA Frontiers in Microbiology 6, Article 773

The Hha family of proteins is involved in the regulation of gene expression in enterobacteria by forming complexes with H-NS-like proteins. Whereas several amino acid residues of both proteins participate in the interaction, some of them play a key role. Residue D48 of Hha protein is essential for the interaction with H-NS, thus the D48N substitution in Hha protein abrogates H-NS/Hha interaction. Despite being a paralog of H-NS protein, StpA interacts with HhaD48N with higher affinity than with the wild type Hha protein. To analyze whether Hha is capable of acting independently of H-NS and StpA, we conducted transcriptomic analysis on the hha and stpA deletion strains and the hhaD48N substitution strain of Salmonella Typhimurium using a custom microarray. The results obtained allowed the identification of 120 genes regulated by Hha in an H-NS/StpA-independent manner, 38% of which are horizontally acquired genes. A significant number of the identified genes are involved in functions related to cell motility, iron uptake, and pathogenicity. Thus, motility assays, siderophore detection and intra-macrophage replication assays were performed to confirm the transcriptomic data. Our findings point out the importance of Hha protein as an independent regulator in S. Typhimurium, highlighting a regulatory role on virulence.

JTD Keywords: Salmonella, Gene regulation, Motility, Pathogenicity island, H-NS, HHA, STPA


Comelles, J., Hortigüela, V., Martínez, Elena, Riveline, D., (2015). Methods for rectifying cell motions in vitro: Breaking symmetry using microfabrication and microfluidics Methods in Cell Biology - Biophysical Methods in Cell Biology (ed. Wilson, L., Tran, P.), Academic Press (Santa Barbara, USA) 125, 437-452

Cell motility is an important phenomenon in cell biology, developmental biology, and cancer. Here we report methods that we designed to identify and characterize external factors which direct cell motions by breaking locally the symmetry. We used microfabrication and microfluidics techniques to impose and combine mechanical and chemical cues to moving fibroblasts. Gradients can thereby be engineered at the cellular scale and this approach has allowed to disentangle roles of the nucleus and protrusion activity in setting cell directions.

JTD Keywords: Adhesion, Biological physics, Cell motility, Gradient, Ratchet