{"id":62377,"date":"2023-09-13T15:42:45","date_gmt":"2023-09-13T13:42:45","guid":{"rendered":"https:\/\/www.embl.org\/news\/?p=62377"},"modified":"2024-03-22T11:44:11","modified_gmt":"2024-03-22T10:44:11","slug":"understanding-how-cells-avoid-obstacles","status":"publish","type":"post","link":"https:\/\/www.embl.org\/news\/science\/understanding-how-cells-avoid-obstacles\/","title":{"rendered":"Understanding how cells avoid obstacles"},"content":{"rendered":"\n<article class=\"vf-card vf-card--brand vf-card--bordered vf-u-margin__bottom--800\" default>\n  <div class=\"vf-card__content | vf-stack vf-stack--400\">\n      <h3 class=\"vf-card__heading\">\n      Summary    <\/h3>\n                <p class=\"vf-card__text\"><ul>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">When migrating cells encounter obstacles, their membrane flattens at the contact.\u00a0<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">EMBL researchers have found that a protein called Snx33 can sense this change in membrane curvature and help destabilise the cytoskeleton locally.<\/span><\/li>\r\n \t<li style=\"font-weight: 400;\" aria-level=\"1\"><span style=\"font-weight: 400;\">This process helps the cell avoid obstacles and move in a different direction. This mechanism might be active in many different types of migrating cells, such as immune or cancer cells. <\/span><\/li>\r\n<\/ul><\/p>\n      <\/div>\n<\/article>\n\n\n\n\n<p>Imagine a dark room packed full of furniture. Now imagine moving through it to get to the other side, using only your toe tips for guidance. While it may seem challenging (or unspeakably tedious) to us, this is a task that many cells in our body perform regularly while migrating through tissues. <a href=\"https:\/\/doi.org\/10.1038\/s41467-023-41173-1\">New research<\/a> from the Diz-Mu\u00f1oz group at EMBL Heidelberg has now identified a novel molecular pathway that helps cells achieve this feat.&nbsp;<\/p>\n\n\n\n<p>Cells often move by first extending a part of their outer membrane and cytoplasm in a chosen direction. This protrusion, called the \u2018leading edge\u2019, is highly dynamic at first but settles as the cell slowly builds up the underlying skeletal structure. This \u2018cytoskeleton\u2019, formed by filaments of a protein called actin, helps stabilise the leading edge and allows the rest of the cell to move in that direction.<\/p>\n\n\n\n<p>However, things get tricky when the leading edge encounters an obstacle, like another cell or a physical barrier. <a href=\"https:\/\/www.embl.org\/groups\/diz-munoz\/\">Alba Diz-Mu\u00f1oz\u2019s group<\/a> at EMBL studies how mechanical interactions at the surface of the cell regulate its behaviours. \u201cWe have something of a material scientist\u2019s view on biology,\u201d Diz-Mu\u00f1oz said. \u201cPhysical properties like fluidity, viscosity, and curvature, particularly at the membrane interface, can influence how a cell reacts to its environment. However, not much is known about how this is coordinated at the molecular level.\u201d<\/p>\n\n\n\n<p>In the new study, published in <em>Nature Communications, <\/em>Diz Mu\u00f1oz\u2019s team has identified a protein \u2013 Snx33 \u2013 as a critical regulator of the process by which cells arrest the progress of the leading edge upon encountering an obstacle. Snx33 belongs to a large family of proteins called BAR-domain proteins, which are known for their ability to sense the curvature of membranes.<\/p>\n\n\n\n<p>When a cell hits an obstacle, the leading edge flattens as a result of this interaction, thus changing the curvature. Through a series of elegant experiments, the researchers showed how Snx33 responds to this change by recruiting molecular machinery that helps inhibit the actin cytoskeleton. This, in turn, helps the cell slowly dissolve the leading edge and make progress in a different direction. Cells from which Snx33 had been genetically deleted, therefore, were slower in navigating environments that were crowded or had barriers.&nbsp;<\/p>\n\n\n\n<p>There are several currently known BAR-domain proteins, which are highly conserved in animal cells. &#8220;From our observations, a picture emerges where the diversity of BAR-domain proteins could allow the cells to decode and react to the information from membrane curvature in unique ways, allowing for quick and complex reactions to various environmental stimuli,&#8221; said Ewa Sitarska, first author of the study and a former PhD student in the Diz-Mu\u00f1oz lab.<\/p>\n\n\n\n<figure class=\"vf-figure wp-block-video\"><video style=\"max-width: 100%;\" controls src=\"https:\/\/www.embl.org\/news\/wp-content\/uploads\/2023\/09\/29-15x500_time_high_d2dish5-01-Lattice_Lightsheet-1-third-cell-movie_SuppVideo2-NO-TEXT.mp4\"><\/video><figcaption class=\"vf-figure__caption\">A migrating neutrophil-like cell, with the cell membrane at the leading edge marked in purple and the curvature-sensing Snx33 protein visible in green. Credit: Ewa Sitarska<\/figcaption><\/figure>\n\n\n\n<p>Diz-Mu\u00f1oz believes that given the ubiquitousness of BAR-domain proteins, other migrating cell types might also use similar navigational mechanisms. This can be highly relevant not only for immune cells, like the neutrophil-like cells from this study, but also for metastasising tumour cells, embryonic cells during development, or even free-living single-celled microbes.&nbsp;<\/p>\n\n\n\n<p>\u201cWe have identified a molecular gatekeeper which basically tells the cell: \u2018You\u2019ve hit an obstacle, go elsewhere,\u2019\u201d said Diz-Mu\u00f1oz. \u201cI think the general principle \u2013 of sensing curvature and activating downstream molecular pathways \u2013 might apply at much wider length and time scales, perhaps even at the level of tissues.\u201d<\/p>\n\n\n\n<p>The study involved collaborations with a number of other EMBL groups, including <a href=\"https:\/\/www.embl.org\/groups\/erzberger\/\">Anna Erzberger<\/a>, <a href=\"https:\/\/www.embl.org\/groups\/kreshuk\/\">Anna Kreshuk<\/a>, and <a href=\"https:\/\/www.embl.org\/groups\/schwab\/\">Yannick Schwab&#8217;s<\/a> groups at EMBL Heidelberg, and <a href=\"https:\/\/www.embl.org\/groups\/kosinski\/\">Jan Kosinski\u2019s<\/a> group at EMBL Hamburg.&nbsp;<\/p>\n\n\n\n<p>The study also provides impetus for further investigations on curvature-sensing proteins. &#8220;Mammalian cells have over 80 different proteins assumed to be sensing curvature and more are still being discovered,\u201d said Sitarska. \u201cOur work provides a hint to how important and widespread this process is. Most of these proteins are still poorly understood and thus, provide a very interesting subject of research.&#8221;<\/p>\n","protected":false},"excerpt":{"rendered":"<p>EMBL researchers have identified a novel mechanism that allows cells to sense obstacles in their path and avoid them while navigating complex environments.<\/p>\n","protected":false},"author":124,"featured_media":62691,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[2,17591],"tags":[65,64,979,5650,43,980],"embl_taxonomy":[19203],"class_list":["post-62377","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-science","category-science-technology","tag-biophysics","tag-cell-biology","tag-cell-membrane","tag-diz-munoz","tag-heidelberg","tag-neutrophil","embl_taxonomy-diz-munoz-group"],"acf":{"vf_locked":false,"featured":true,"show_featured_image":false,"field_target_display":"embl","field_article_language":{"value":"english","label":"English"},"article_intro":"<p>EMBL researchers have identified a novel mechanism that allows cells to sense obstacles in their path and avoid them while navigating complex environments<\/p>\n","related_links":[{"link_description":"Making patterns visible","link_url":"https:\/\/www.embl.org\/news\/science\/making-patterns-visible\/"},{"link_description":"Scratching the surface on cell differentiation","link_url":"https:\/\/www.embl.org\/news\/science\/scratching-the-surface-on-cell-differentiation\/"},{"link_description":"Diz-Mu\u00f1oz research group","link_url":"https:\/\/www.embl.org\/groups\/diz-munoz\/"},{"link_description":"Cell Biology and Biophysics unit","link_url":"https:\/\/www.embl.org\/research\/units\/cell-biology-biophysics\/"}],"source_article":[{"publication_title":"Sensing their plasma membrane curvature allows migrating cells to circumvent obstacles","publication_link":{"title":"","url":"https:\/\/doi.org\/10.1038\/s41467-023-41173-1","target":""},"publication_authors":"Sitarska, E., et al.","publication_source":"Nature Communications","publication_date":"13 September 2023","publication_doi":"doi.org\/10.1038\/s41467-023-41173-1"}],"in_this_article":false,"press_contact":"None","article_translations":false,"languages":""},"embl_taxonomy_terms":[{"uuid":"a:3:{i:0;s:36:\"302cfdf7-365b-462a-be65-82c7b783ebf7\";i:1;s:36:\"64999cc4-9a7c-4fea-8339-0e2acc990e08\";i:2;s:36:\"121be34d-dc2b-49fb-8b15-0745ad7211a0\";}","parents":[],"name":["Diz-Mu\u00f1oz Group"],"slug":"diz-munoz-group","description":"What &gt; 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