Membrane-Mediated Cooperative Interactions of CD47 and SIRP<i>α</i>
The specific binding of the ubiquitous ‘marker of self’ protein CD47 to the SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> protein anch...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Membranes |
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| Online Access: | https://www.mdpi.com/2077-0375/13/11/871 |
| _version_ | 1797458464036880384 |
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| author | Long Li Chen Gui Jinglei Hu Bartosz Różycki |
| author_facet | Long Li Chen Gui Jinglei Hu Bartosz Różycki |
| author_sort | Long Li |
| collection | DOAJ |
| description | The specific binding of the ubiquitous ‘marker of self’ protein CD47 to the SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> protein anchored in the macrophage plasma membrane results in the inhibition of the engulfment of ‘self’ cells by macrophages and thus constitutes a key checkpoint of our innate immune system. Consequently, the CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> protein complex has been recognized as a potential therapeutic target in cancer and inflammation. Here, we introduce a lattice-based mesoscale model for the biomimetic system studied recently in fluorescence microscopy experiments where GFP-tagged CD47 proteins on giant plasma membrane vesicles bind to SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> proteins immobilized on a surface. Computer simulations of the lattice-based mesoscale model allow us to study the biomimetic system on multiple length scales, ranging from single nanometers to several micrometers and simultaneously keep track of single CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> binding and unbinding events. Our simulations not only reproduce data from the fluorescence microscopy experiments but also are consistent with results of several other experiments, which validates our numerical approach. In addition, our simulations yield quantitative predictions on the magnitude and range of effective, membrane-mediated attraction between CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> complexes. Such detailed information on CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> interactions cannot be obtained currently from experiments alone. Our simulation results thus extend the present understanding of cooperative effects in CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> interactions and may have an influence on the advancement of new cancer treatments. |
| first_indexed | 2024-03-09T16:37:29Z |
| format | Article |
| id | doaj.art-b63a8e580fe6478d97000c504b9c6b45 |
| institution | Directory Open Access Journal |
| issn | 2077-0375 |
| language | English |
| last_indexed | 2024-03-09T16:37:29Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Membranes |
| spelling | doaj.art-b63a8e580fe6478d97000c504b9c6b452023-11-24T14:55:16ZengMDPI AGMembranes2077-03752023-11-01131187110.3390/membranes13110871Membrane-Mediated Cooperative Interactions of CD47 and SIRP<i>α</i>Long Li0Chen Gui1Jinglei Hu2Bartosz Różycki3Kuang Yaming Honors School, Nanjing University, Nanjing 210023, ChinaKuang Yaming Honors School, Nanjing University, Nanjing 210023, ChinaKuang Yaming Honors School, Nanjing University, Nanjing 210023, ChinaInstitute of Physics, Polish Academy of Sciences, Aleja Lotników 32/46, 02-668 Warsaw, PolandThe specific binding of the ubiquitous ‘marker of self’ protein CD47 to the SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> protein anchored in the macrophage plasma membrane results in the inhibition of the engulfment of ‘self’ cells by macrophages and thus constitutes a key checkpoint of our innate immune system. Consequently, the CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> protein complex has been recognized as a potential therapeutic target in cancer and inflammation. Here, we introduce a lattice-based mesoscale model for the biomimetic system studied recently in fluorescence microscopy experiments where GFP-tagged CD47 proteins on giant plasma membrane vesicles bind to SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> proteins immobilized on a surface. Computer simulations of the lattice-based mesoscale model allow us to study the biomimetic system on multiple length scales, ranging from single nanometers to several micrometers and simultaneously keep track of single CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> binding and unbinding events. Our simulations not only reproduce data from the fluorescence microscopy experiments but also are consistent with results of several other experiments, which validates our numerical approach. In addition, our simulations yield quantitative predictions on the magnitude and range of effective, membrane-mediated attraction between CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> complexes. Such detailed information on CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> interactions cannot be obtained currently from experiments alone. Our simulation results thus extend the present understanding of cooperative effects in CD47–SIRP<inline-formula><math xmlns="http://www.w3.org/1998/Math/MathML" display="inline"><semantics><mi>α</mi></semantics></math></inline-formula> interactions and may have an influence on the advancement of new cancer treatments.https://www.mdpi.com/2077-0375/13/11/871membrane adhesionbiomimeticscomputer simulationsCD47SIRP<i>α</i> |
| spellingShingle | Long Li Chen Gui Jinglei Hu Bartosz Różycki Membrane-Mediated Cooperative Interactions of CD47 and SIRP<i>α</i> Membranes membrane adhesion biomimetics computer simulations CD47 SIRP<i>α</i> |
| title | Membrane-Mediated Cooperative Interactions of CD47 and SIRP<i>α</i> |
| title_full | Membrane-Mediated Cooperative Interactions of CD47 and SIRP<i>α</i> |
| title_fullStr | Membrane-Mediated Cooperative Interactions of CD47 and SIRP<i>α</i> |
| title_full_unstemmed | Membrane-Mediated Cooperative Interactions of CD47 and SIRP<i>α</i> |
| title_short | Membrane-Mediated Cooperative Interactions of CD47 and SIRP<i>α</i> |
| title_sort | membrane mediated cooperative interactions of cd47 and sirp i α i |
| topic | membrane adhesion biomimetics computer simulations CD47 SIRP<i>α</i> |
| url | https://www.mdpi.com/2077-0375/13/11/871 |
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