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Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2026,9,22]]},"abstract":"<jats:p>\n                    The \u201cbrain-eating amoeba\u201d\n                    <jats:italic toggle=\"yes\">Naegleria fowleri<\/jats:italic>\n                    dwells in ponds where it normally feeds on bacteria, but if it enters the brain it can cause a deadly infection. To establish infection,\n                    <jats:italic toggle=\"yes\">N. fowleri<\/jats:italic>\n                    must migrate through different environments\u2014along olfactory axons, through openings in the cribriform plate, and within brain tissue\u2014yet how it does so remains unknown. As a model for\n                    <jats:italic toggle=\"yes\">N. fowleri<\/jats:italic>\n                    migration within these environments, we examine how its nonpathogenic relative,\n                    <jats:italic toggle=\"yes\">Naegleria gruberi<\/jats:italic>\n                    , navigates environments of distinct geometries. We show that\n                    <jats:italic toggle=\"yes\">Naegleria<\/jats:italic>\n                    uses both actin-rich protrusions and membrane blebs to crawl across or between flat surfaces. We also explore how\n                    <jats:italic toggle=\"yes\">Naegleria<\/jats:italic>\n                    interact with narrow channels and find that, unlike\n                    <jats:italic toggle=\"yes\">Dictyostelium<\/jats:italic>\n                    amoebae that we show frequently disengage from channel interfaces,\n                    <jats:italic toggle=\"yes\">Naegleria<\/jats:italic>\n                    amoebae probe channels until they enter. Once inside,\n                    <jats:italic toggle=\"yes\">Naegleria<\/jats:italic>\n                    crawls quickly (&gt;50 \u03bcm\/min) and unidirectionally over long distances (&gt;1 mm) using only bleb-based motility. We also introduced\n                    <jats:italic toggle=\"yes\">Naegleria<\/jats:italic>\n                    to granular hydrogel matrices that mimic pond sediments and found that cells readily enter and migrate through these three-dimensional matrices using both blebs and lamellar protrusions. Although cells in matrices showed lower persistence at short timescales, longer time scales correlate with increased persistence, suggesting\n                    <jats:italic toggle=\"yes\">Naegleria<\/jats:italic>\n                    cells may retain memory of past orientation. We propose that pond life may select for three behaviors that prime\n                    <jats:italic toggle=\"yes\">Naegleria<\/jats:italic>\n                    for pathogenesis: memory-guided motility that would facilitate exploration of sinus cavities, confinement-seeking (\u201cclaustrophilia\u201d) that would promote entry into narrow passages along olfactory axons, and persistent bleb-based migration that would allow rapid transit along axons to the brain.\n                  <\/jats:p>","DOI":"10.1073\/pnas.2534165123","type":"journal-article","created":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T17:02:36Z","timestamp":1789059756000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":0,"title":["<i>Naegleria<\/i>\n                    amoebae seek confinement and crawl persistently through narrow spaces"],"prefix":"10.1073","volume":"123","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9985-9522","authenticated-orcid":false,"given":"Katrina B.","family":"Velle","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/00fzmm222","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Biology, University of Massachusetts Dartmouth","place":["North Dartmouth"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9220-2256","authenticated-orcid":false,"given":"Meera","family":"Ramaswamy","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/017zqws13","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Mechanical Engineering, University of Minnesota","place":["Minneapolis"]},{"id":[{"id":"https:\/\/ror.org\/00hx57361","id-type":"ROR","asserted-by":"publisher"}],"name":"Princeton Center for Complex Materials, Princeton 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