{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T06:19:29Z","timestamp":1787897969367,"version":"build-2784847793"},"reference-count":46,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell Dev. Biol."],"abstract":"<jats:p>\n                    The coexistence of multiple actin crosslinking proteins in cells suggests that crosslinkers with distinct binding dynamics may cooperate to organize F-actin networks that support adhesion, motility, and division. Here, we examine how crosslinker identity and lifetime regulate actin-network structure and mechanics using a reconstituted system that combines\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m1\">\n                        <mml:mrow>\n                          <mml:mi>\u03b1<\/mml:mi>\n                        <\/mml:mrow>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    -actinin, a native dynamic actin crosslinker, with biotin\u2013NeutrAvidin, a non-native model of long-lived, effectively persistent crosslinking. Using confocal fluorescence microscopy and optical-tweezers microrheology, we compared networks formed with\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m2\">\n                        <mml:mrow>\n                          <mml:mi>\u03b1<\/mml:mi>\n                        <\/mml:mrow>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    -actinin alone, biotin\u2013NeutrAvidin alone, or a representative equimolar 50:50 mixture of the two crosslinking schemes at fixed total crosslinker-to-actin ratio,\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m3\">\n                        <mml:mrow>\n                          <mml:mi>R<\/mml:mi>\n                        <\/mml:mrow>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    . Mixed crosslinking produced the strongest mesoscale structural heterogeneity at high\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m4\">\n                        <mml:mrow>\n                          <mml:mi>R<\/mml:mi>\n                        <\/mml:mrow>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    , yielding larger characteristic structural features than either pure-crosslinker network. However, this structural coarsening did not translate into uniformly enhanced linear viscoelasticity: mixed networks generally exhibited moduli and viscosities intermediate between those of pure\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m5\">\n                        <mml:mrow>\n                          <mml:mi>\u03b1<\/mml:mi>\n                        <\/mml:mrow>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    -actinin and biotin\u2013NeutrAvidin networks. Nonlinear microrheology further revealed that crosslinker identity and lifetime regulate force buildup, strain stiffening, and stress relaxation in an observable-dependent manner. Thus, the representative mixed-crosslinker network did not simply generate the strongest or most solid-like actin network. Instead, its effects were selective: it enhanced mesoscale heterogeneity at high\n                    <jats:inline-formula>\n                      <mml:math xmlns:mml=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"m6\">\n                        <mml:mrow>\n                          <mml:mi>R<\/mml:mi>\n                        <\/mml:mrow>\n                      <\/mml:math>\n                    <\/jats:inline-formula>\n                    , produced intermediate linear and total nonlinear force responses, and gave rise to distinct nonlinear stiffening and relaxation behavior. These results demonstrate that cooperation between dynamic and persistent crosslinks is deformation-regime dependent, providing a mechanism for tuning actin-network architecture and mechanics without uniformly increasing rigidity.\n                  <\/jats:p>","DOI":"10.3389\/fcell.2026.1900481","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T05:35:41Z","timestamp":1787895341000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Crosslinker identity and dynamics regulate F-actin network structure and mechanics"],"prefix":"10.3389","volume":"14","author":[{"given":"Lauren","family":"Godfrey","sequence":"first","affiliation":[{"name":"Department of Physics and Astronomy, Bucknell University","place":["Lewisburg, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bekele J.","family":"Gurmessa","sequence":"additional","affiliation":[{"name":"Department of Physics and Astronomy, Bucknell University","place":["Lewisburg, PA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,28]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1152\/physrev.00018.2013","article-title":"Actin dynamics, architecture, and mechanics in cell motility","volume":"94","author":"Blanchoin","year":"2014","journal-title":"Physiol. 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