A Hybrid Cellular Automata Model of Multicellular Tumour Spheroid Growth in Hypoxic Microenvironment

<table class="table-group" id="tab2"><tr><td><table class="table"><tr><td class="thead-hr" colspan="4"><hr/></td></tr><tr class="thead"><td align="left">Phenotypes</td><td align="center">MDE production</td><td align="center">Oxygen consumption</td><td align="center"><span style="width: 17.575001px;"><svg height="16.799999" id="M43" style="vertical-align:-3.3907pt" version="1.1" viewbox="0 0 17.575001 16.799999" width="17.575001" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
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<g transform="matrix(.012,-0,0,-.012,13.087,16.038)"><path d="M244 607q0 -25 -15.5 -43t-37.5 -18q-19 0 -32 13t-13 35q0 21 15 41t39 20q20 0 32 -14t12 -34zM222 91q-29 -33 -79 -68t-75 -35q-13 0 -19 7.5t-6 31t10 65.5l62 253q5 26 -1 26q-21 0 -72 -43l-13 24q43 40 91 68t71 28q30 0 10 -78l-71 -274q-8 -30 3 -30
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</svg></span></td></tr><tr><td class="thead-hr" colspan="4"><hr/></td></tr><tr><td align="left">Proliferating cells (P)</td><td align="center"><span style="width: 19.225px;"><svg height="13.8875" id="M44" style="vertical-align:-4.0404pt" version="1.1" viewbox="0 0 19.225 13.8875" width="19.225" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.625,8.238)"><path d="M538 96q-38 -45 -84 -76.5t-71 -31.5q-44 0 -15 117q12 49 18 89h-2q-99 -128 -163 -178q-36 -28 -70 -28q-26 0 -44 38h-2q-16 -69 -16 -129q0 -43 11 -75.5t24 -42.5l1 -6q-7 -12 -24.5 -23t-37.5 -11q-40 0 -40 76q0 52 35 202l94 407l78 24l5 -5q-32 -122 -72 -310
q-7 -33 0 -55t25 -22q36 0 105.5 75t107.5 145l32 146l75 26h10q-50 -197 -78 -347q-7 -38 6 -38q7 0 31 17t47 39z" id="x1D707"></path></g>
<g transform="matrix(.012,-0,0,-.012,10.062,13.275)"><path d="M649 676l-22 -187l-33 -2q3 56 -12 94q-8 20 -31.5 26.5t-86.5 6.5h-74l-90 -491q-4 -23 -6 -36.5t1 -25t7 -16.5t18 -9t27 -5t41 -3l-6 -28h-286l4 28q68 5 84 18.5t28 76.5l94 491h-55q-74 0 -100.5 -6t-41.5 -23q-24 -29 -54 -98l-32 1q32 98 53 188h22q7 -18 15 -22
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</svg></span></td><td align="center"><span style="width: 9.7624998px;"><svg height="13.3" id="M45" style="vertical-align:-3.56265pt" version="1.1" viewbox="0 0 9.7624998 13.3" width="9.7624998" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.625,8.238)"><path d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5
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</svg></span></td><td align="center">2</td></tr><tr><td align="left">Quiescent cells (Q)</td><td align="center"><span style="width: 34.387501px;"><svg height="18.225" id="M46" style="vertical-align:-4.0404pt" version="1.1" viewbox="0 0 34.387501 18.225" width="34.387501" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.625,12.575)"><path d="M538 96q-38 -45 -84 -76.5t-71 -31.5q-44 0 -15 117q12 49 18 89h-2q-99 -128 -163 -178q-36 -28 -70 -28q-26 0 -44 38h-2q-16 -69 -16 -129q0 -43 11 -75.5t24 -42.5l1 -6q-7 -12 -24.5 -23t-37.5 -11q-40 0 -40 76q0 52 35 202l94 407l78 24l5 -5q-32 -122 -72 -310
q-7 -33 0 -55t25 -22q36 0 105.5 75t107.5 145l32 146l75 26h10q-50 -197 -78 -347q-7 -38 6 -38q7 0 31 17t47 39z" id="x1D707"></path></g>
<g transform="matrix(.012,-0,0,-.012,10.062,17.6)"><path d="M649 676l-22 -187l-33 -2q3 56 -12 94q-8 20 -31.5 26.5t-86.5 6.5h-74l-90 -491q-4 -23 -6 -36.5t1 -25t7 -16.5t18 -9t27 -5t41 -3l-6 -28h-286l4 28q68 5 84 18.5t28 76.5l94 491h-55q-74 0 -100.5 -6t-41.5 -23q-24 -29 -54 -98l-32 1q32 98 53 188h22q7 -18 15 -22
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<g transform="matrix(.017,-0,0,-.017,18.6,12.575)"><path d="M368 703l-264 -866h-60l265 866h59z" id="x2F"></path></g><g transform="matrix(.017,-0,0,-.017,25.603,12.575)"><path d="M153 550l-26 -186q79 31 111 31q90 0 141.5 -51t51.5 -119q0 -93 -89 -166q-85 -69 -173 -71q-32 0 -61.5 11.5t-41.5 23.5q-18 17 -17 34q2 16 22 33q14 9 26 -1q61 -50 124 -50q60 0 93 43.5t33 104.5q0 69 -41.5 110t-121.5 41q-53 0 -102 -20l38 305h286l6 -8
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</svg></span></td><td align="center"><span style="width: 24.924999px;"><svg height="17.637501" id="M47" style="vertical-align:-3.56265pt" version="1.1" viewbox="0 0 24.924999 17.637501" width="24.924999" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.625,12.575)"><path d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5
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</svg></span></td><td align="center">4</td></tr><tr><td align="left">Necrotic cells (N)</td><td align="center"><span style="width: 42.549999px;"><svg height="18.225" id="M48" style="vertical-align:-4.0404pt" version="1.1" viewbox="0 0 42.549999 18.225" width="42.549999" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.625,12.575)"><path d="M538 96q-38 -45 -84 -76.5t-71 -31.5q-44 0 -15 117q12 49 18 89h-2q-99 -128 -163 -178q-36 -28 -70 -28q-26 0 -44 38h-2q-16 -69 -16 -129q0 -43 11 -75.5t24 -42.5l1 -6q-7 -12 -24.5 -23t-37.5 -11q-40 0 -40 76q0 52 35 202l94 407l78 24l5 -5q-32 -122 -72 -310
q-7 -33 0 -55t25 -22q36 0 105.5 75t107.5 145l32 146l75 26h10q-50 -197 -78 -347q-7 -38 6 -38q7 0 31 17t47 39z" id="x1D707"></path></g>
<g transform="matrix(.012,-0,0,-.012,10.062,17.6)"><path d="M649 676l-22 -187l-33 -2q3 56 -12 94q-8 20 -31.5 26.5t-86.5 6.5h-74l-90 -491q-4 -23 -6 -36.5t1 -25t7 -16.5t18 -9t27 -5t41 -3l-6 -28h-286l4 28q68 5 84 18.5t28 76.5l94 491h-55q-74 0 -100.5 -6t-41.5 -23q-24 -29 -54 -98l-32 1q32 98 53 188h22q7 -18 15 -22
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<g transform="matrix(.017,-0,0,-.017,18.6,12.575)"><path d="M368 703l-264 -866h-60l265 866h59z" id="x2F"></path></g><g transform="matrix(.017,-0,0,-.017,25.603,12.575)"><path d="M384 0h-275v27q67 5 81.5 18.5t14.5 68.5v385q0 38 -7.5 47.5t-40.5 10.5l-48 2v24q85 15 178 52v-521q0 -55 14.5 -68.5t82.5 -18.5v-27z" id="x31"></path></g><g transform="matrix(.017,-0,0,-.017,33.763,12.575)"><path d="M241 635q53 0 94 -28.5t63.5 -76t33.5 -102.5t11 -116q0 -58 -11 -112.5t-34 -103.5t-63.5 -78.5t-94.5 -29.5t-95 28t-64.5 75t-34.5 102.5t-11 118.5q0 58 11.5 112.5t34.5 103t64.5 78t95.5 29.5zM238 602q-32 0 -55.5 -25t-35.5 -68t-17.5 -91t-5.5 -105
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</svg></span></td><td align="center"><span style="width: 24.924999px;"><svg height="17.637501" id="M49" style="vertical-align:-3.56265pt" version="1.1" viewbox="0 0 24.924999 17.637501" width="24.924999" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.625,12.575)"><path d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5
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</svg></span></td><td align="center">6</td></tr><tr><td align="left">Mutated cells (M)</td><td align="center"><span style="width: 42.549999px;"><svg height="18.225" id="M50" style="vertical-align:-4.0404pt" version="1.1" viewbox="0 0 42.549999 18.225" width="42.549999" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.625,12.575)"><path d="M456 178h-96v-72q0 -51 12.5 -62.5t72.5 -16.5v-27h-256v27q65 5 78 17t13 62v72h-260v28q182 271 300 426h40v-407h96v-47zM280 225v295h-2q-107 -148 -196 -295h198z" id="x34"></path></g><g transform="matrix(.017,-0,0,-.017,8.784,12.575)"><path d="M368 703l-264 -866h-60l265 866h59z" id="x2F"></path></g><g transform="matrix(.017,-0,0,-.017,15.788,12.575)"><path d="M285 378v-2q65 -13 102 -54.5t37 -97.5q0 -57 -30.5 -104.5t-74 -75t-85.5 -42t-72 -14.5q-31 0 -59.5 11t-40.5 23q-19 18 -16 36q1 16 23 33q13 10 24 0q58 -51 124 -51q55 0 88 40t33 112q0 64 -39 96.5t-88 32.5q-29 0 -64 -11l-6 29q77 25 118 57.5t41 84.5
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<g transform="matrix(.012,-0,0,-.012,33.375,17.6)"><path d="M649 676l-22 -187l-33 -2q3 56 -12 94q-8 20 -31.5 26.5t-86.5 6.5h-74l-90 -491q-4 -23 -6 -36.5t1 -25t7 -16.5t18 -9t27 -5t41 -3l-6 -28h-286l4 28q68 5 84 18.5t28 76.5l94 491h-55q-74 0 -100.5 -6t-41.5 -23q-24 -29 -54 -98l-32 1q32 98 53 188h22q7 -18 15 -22
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<g transform="matrix(.017,-0,0,-.017,.625,11.413)"><path d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" id="x32"></path></g><g transform="matrix(.017,-0,0,-.017,8.784,11.413)"><path d="M478 372q0 -39 -31 -97t-61 -98t-78 -98q-45 -55 -73 -102q-13 -79 -13 -197q-11 -11 -43.5 -25.5t-53.5 -15.5l-15 17q5 35 26 101.5t47 123.5q8 72 -1.5 174.5t-37.5 178.5q-14 37 -29 37q-20 0 -67 -65l-25 21q37 60 73 90.5t63 30.5q47 0 72 -112q13 -56 17.5 -141.5
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</svg></span></td><td align="center">0</td></tr><tr class="table-tr"><td colspan="4"><hr class="tbody-hr"/></td></tr></table></td></tr></table>

Parameters of the four different phenotypes.

Journal of Applied Mathematics

tab2

Table 2

Table 2: A Hybrid Cellular Automata Model of Multicellular Tumour Spheroid Growth in Hypoxic Microenvironment 