Assay to Measure Cell Traction Forces for High Throughput Drug Screening and Mechanical Phenotyping
Application
Mechanically induced catalytic amplification reaction (MCR) as an assay for high throughput screening of drugs which target cellular mechanics and mechanical phenotyping of live cells.
Key Benefits
- Adaptable for high throughput screening of drugs that impair cell mechanics.
- Enables characterization of different cells types based on their traction forces.
- Assay can be performed using a conventional fluorescence plate reader.
- Allows detection of weak and transient cellular forces.
Market Summary
High Throughput Screening (HTS) is a drug-discovery process widely used in the pharmaceutical industry. It leverages automation to quickly assay the biological or biochemical activity of a large number of drug-like compounds. HTS of drugs that target mechanical processes and screening the mechanical phenotype of a library of cells is expensive and challenging. Current assays for the measurement and quantification of receptor-mediated forces in cells require high-end microscopy systems which are less affordable in general molecular biology labs. Therefore, there is a pressing need to develop strategies and toolkits that can easily translate receptor-mediated forces into an easily quantifiable and amplified chemical signal to allow rapid drug screening.
Technical Summary
Emory inventors have developed a low cost and quick assay to measure receptor mediated forces using mechanically induced catalytic amplification reaction (MCR). The assay is akin to PCR or ELISA for cell traction forces. The assay involves use of labile DNA duplexes with ligands that are immobilized on surfaces. Mechanical force acting on a ligand via its cognate receptor denatures the duplex thereby exposing a blocked primer. Amplification of primers is achieved using an isothermal polymerization reaction and quantified by fluorescence readout. This unique technology can be used to rapidly quantify cell traction forces using a conventional fluorescence plate reader. The researchers have demonstrated screening of a small library of antibodies and small molecules that inhibit cell traction forces across different cell types. The assay can be easily used to characterize cell tumor subtypes and elucidate the differences in their traction stresses. The catalytic amplification of signal allows detection of weak and transient mechanical forces which are otherwise difficult to quantify. MCR may also serve as a powerful tool for high throughput screening of drugs that target cellular mechanics.
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f0m/nq1hf8t9R/4vG/JcqLuhZDjLsTCPYS550/7ZVzo3S7MK/JueymsZArAZRMfow8b3uc1nudv/dTsGfPKfDPlpYY6njlPHMfvbQ/eRKMdwQTp03r0/8ARf/S9NzstmFjnIe11gDmMDGAFxdY9tLGtaS38+xZ3/Oro4A3vew6At2OcQ5zhVXT+h9Tdc+w7PSZ+5Z6i0OoWZFWI9+NWLbhGxhEiSR2ELEu6j1au/7K/pdDcnKtLKDu3sIDS997y1ge+unbV69lv2b+c2Vfpf5xKdC/6x9IofdXbeWux9bZY+Gjf6H0tu136Rtn/bN3+iTY/wBZelZFrKWPf6ljxXW01u1Ltxqdua1zWNtrqstZ6uz9FWhtzOq2+s6zpTazWxzqy94eS9pre1ntZ9Gzc+2t7f3P5r1lBuV1eioR0qt9rAdvpuDQ5zi+wNb7Heju/wAJY9/p+skpJX9YOg7i+t+1172tcfSc0ve5rdm6WDe7Z6VX/XKKv8LUmd9ZejDFdlWOc30anX+mWEv2tPo2Nrj2usbb+gc1j/pqu3qWZkZXoVdLra9gbZbXZG/0nNNfuOz06rLtvpU12O3/AKD9LWyiz1U9edmXYzLWdKbUXhtrbCwvAYR6W4U7K73XV0u9P0fY99f/AASSnea7c0OiJEwedU6FULH4zJHoWOY2Wtj2GNWiZb7FQyKsrDDr35l1vqOZWxlbWFxc92xrf036Fv0/+CQPkp1Elg09awby30+q2lrgCbPTZsaSdgZbZ6O2t+79/wD0dv8AorE7Or4jwD+0b2k8NdS0OgvdRU7b6Hu+0XM9LG2/0iz9HV70teyndSWEzq+I6n1XdSurbpo6pky4vDK/bQ79M91Vn6D+e/4NSPVcJrmMf1Wxjnna1rq2DXc2t3+A9vpvfV63/cf1afX9L1WJa9lO4q+fXfbh3VY5Lbnsc2twdsIcR7XB+u3amwH22YwNri94fYwuIAJ2PfWJ2+381VvrE6hvSL/tF/2Ws7JtA3HR7Xen6ct9T1dvp7Pof6T9Gipr3YvXrX00tym0MG9z3tP6WQ5/uhzLG3VbX0urr/Q/uXIbel9e9Nlrs3ZlhpfY1r3vqdb6dTG1ena0MZiOyPtG/wDR+p6X83+m/S1UrqunB0V35jnsaHO2je8sJuruxWuaWv8AXt+wXU2W+/8AV6q/9Hj21ToH1esue2rIyA2oAva0vLD6r7a2vr9IO9T+gXfpG+pV9lSU9BS3MF73XOr9EtZ6dbAdzXQfW32u/nG7v5v9HWo2/wDKGP8A8Xb+Wlc/Q/oNduNljqORdUN1wc4u9Ehu+9+VaQytvpVNuZ+k/o1NVlX5l62qcvHzMjEycZ/qUvru2vAImHVMP0gPzmoHopvwknSRU//T9VTQFC2+mms2XPbXW3l7yGtH9pyoWdbpdS67ErffWAYud+ip00/nr9vqV7vz8WrJSU6UAdkHKy8TEqN+XayipvNlrg1v+c+Fy2f9b6a6ybr7GtcGBoxayyvfa31KqX5+Y3d+kr/m7asbF/7cWJkWHNe26l1ZpLS653qPL2RW2h9dnUby+2yre+z0qbv567/R1/zKWmQezb9aejutcwWOFbGh773NLa2tMbbH+pts9H3t/T+n9n/4VazXMe0PaQ5rgC1w1BB4grzirq4ssfWym6y7F3P9EV1yLGFmyz059mQ+j0m021epdj+p6f8Aglt9Ivbi0WXNu+wZFjvUtodNuI57yQ+up7Nnr37v02RkYfp+n6363X+j9JJUZWaL1yp9VcG4bpxRmgubNDhuB9w97mhlzvZ9L20v/wDRijj9TabWYuaw4mW+dlbjuZZH0vsuRDW3f8W5tWT/AKTGrV2QUlzzlp6jfiPrt6VS1t9YdZUWu2zY+9hqvfR+ldsx66PtLWU2et62z+aU/tljca2y/pDGC+xrW1vaGm11ltrN1rK68l+70WMts/R2/wA7/o/0q6CAlASU847Jtbaxw+r4ElrnHY0v2bX7WBzKvTbk7DWytnqfZ9/2inIycSr0MjI1OnU0ZOK3IvwGYlr9HUua0uDWOPpbjsZ/Xb7fYr8BJJTV6Yf1ST/pbv8Az7YrLmtc0tcA5pEEHUEFZ2Dl+lQWeja+LLfcxstM2WHQyrH2/wD7r5H+Z/tQB0TSX7HiemKjTWawNuwtBEe72x/bf/nqFvT8G0NFlFbg0tcAWiJYXOr0/O2Otsez+Wo/b9P6Nkf5n+1Cz7a7LMXEdYaXZL9zeQ79Ftt+kPzt/p+z/wA+M/RooOjYOBgEhxxqi4FpB2NkFntr7f4P8xAdhbc/GspmuiqtzfTZ7WiNuxoY32+/d/4EstvWb7fWONeLb8f1BkUWg1N9Jh9uRjOa17n2Vsfvt9L1GWWepTvo/QoY68wYzWYtrvScHPbbc2wPLGkWn033A+v9prf+p5Ff6Oz/AAX8x6SVWjiemTqt08ZIwqW5QIyGtAskhxJGm4ub7fcrKSX/1Oja/P6cG05FP2rqQZLLrx6l5Ldb7cK+wjHzK9XuqppbiZOMz0vWwrfUWZ1HEu+sRuzcW2zIohga5zTWTdRu2W1U7tzLthu31PZj/n/zd3pLv8jGoyajTkVttqdEscARpxz+6sPK6JmYtwyenWWWFgj6Q+0Bo+jX6t36LqFDd38x1D9Iz+dqy/VVY+9i11z4/wDx/GP/AFN/0/8AaJIEuvD/ANF53I6X1bHxaD1BjHZr/VbWC92x3qlx9Ompnup/Q+lXbvr9Bnp7PU/Srn8L0Wu25VrxiZDrm49Vb3V1sLTsur/S1b7HVb/SYx7f539/8ztrsrC6jYD1BlwyyH4Yfh7x6m4Ot+zX4tp9XCv9Ouy39absp/nac5Ca2t2S+iitljTW1v2Y1syLGhjmurpdVgtqxsTHrf76qsjLsxvU9T9Ekec5cV6uKR2xxEpZv/Co/rP8ZYcMr8B32czA6S8tbj9O2Pv315G13uY6qsvpcz1ttbqMd3pej7/V9V7P57/ArVowsKu70zeMwjcMnGxK987j+iouypZjt/wtlvrOqt/8E9UwxMnJP6exnpcEZT23kbQGtYzp+Ga+nV7Y+n6livY3TenGxoy7ftcgNZVc5oqn81jMOv0sb/Pqss/4RVjz2ScxjxY/bMjw8WbeP/Ucf/q2DIMMQNTddv8Avmtb1S7Pa/BpoqfVAaaGt+2P2z7PtDvZgYlnt/w92QtXpdOdi9MbXYH23tc8tbfYHP2Osc+plt7GuZurqc1vt3/8ZZ/OK9XWytoZWAxjRDWtEADwDQpq3ixTiTKeWWWR02jDHH+5CP8A3eSaCR0ADnU5vUnOe12NWXNdt2i0AjTdtd/Of98RTkdRGpxGR/xw/wDSarO+r+O651xuta5z3PHpkMje597ml1bWvf8AprN7N/8AN/8AbnqCZ9WMQCsOuus9Op9IdY71Hbbam41vvt9R3+Dbaz/R2et/grPTU1eJQ3vtHUv+4jf+3h/6TSGT1E/9pGac/ph/6TVN31doAHo5ORWQ4PMP+k4MfU31DG//AAjn2bf5xCd9WpxPTGU/7UWhptdJr+ia3N+z7v5n3eq2r1P52nH9/wCiSrxU6nT6rKsYMtaGP3vcWgyBue+z6X9pWE1bdjGtknaAJOpMaaqSKllidbtc19tlDHWWUVgOPtIa9zh9nprqsLfWvyHP2+lv/SM9On9H69dq3Fk9Rx20+pm32sbj4xGRWLSGtbaCd77nu9jq9mz0N3vrf/N/4H00g/Vx46bRi49L7A/Cb6mLjWFrmWD1trr8e2hw935v6Z/o+j6f6b9L6frQe6vKxmD03ZL8iui2nGY8tJscbnPxq2fzdFfTmPossZuo/R/0239JWrAy/qz6zX2dSY3Mc42MtqgFjWt9F1LXOreyunbd6dX0Lf8AR2eoxWK+t9Cx8ux2NnV2Pso3Orc4NYdjtuPt2MbXXuc+5j/Yhxx/eH2qqTvM3bRv+lAn4qS5jqH1hqy8R+O3MpwHPLf1rHyG2WMAezc6ut1Pv9u7+wugw87Dzq3W4dzL62uLHOYZAcNS0/yvckJAnQgrq0f/1fVUkkklNPM6T03Otrty8au+ykzW94BI0e2P5TP0r/0b/wBGsX60Nua3D6dis2Yjm2W21UisT6TqBTS6m/ZRdhu9Z/2nH302W7K/0vp+qyzpVndW6VbnPqupubVbS17AHsL2ObZ6bnNdtfVY12+iv3ts/wCtppGhI3KR4vM09W6ziVimihnot+iw03Vgf1W49PUK2/2bU2R1Lq+dWasqhjqjr6f2ey1pP8puW3ptP+e5aTejdaA99OMXd9l7/wAlmL/35I9G62YDa8VknVz7nugeIrZjV7/+3WKH2tb4Bxd19ju2fqlblfZsjEyC5zMV7W45sc11grexluy00/of0djrGVMr3+nR6VfqWLeVDpPS3dPbcbLvWtvcHPIbsYA1oqY2tm6x/wBFvu9S21X1OLoWxlSSSSKlJJJJKUkkq3ULcqrHDsSsW3Gypm0iQGPsrrvsjcz+ZodZb9P8xJTZVfOx2ZOLZTZYaWmHeq0gFpaRY1/6QOZ7XM/OWa3rPVBUzd0q190NFgb7W7iCf0e5rv5L373exnqM9T7V6WNkJ3VeoWNNV3SLNlhexzXODgWtca3+oGscz9Mz+Z/wVm/9K+qj1b6wQCCCLB0IUj6d0y7JY7qBzL2HKg1AsqDhQ2fs24Op9vqb35Lm/mev6f8Ag09/1WrvuN7+oZbLnAMdZWamksAI9H+YLfT97/7b1I9W60a2Ob0wVl4mbLDDfaHu3tFPs9zm1sfZ6f8Ah/V9P0vSv08DL+24dWX6bqW3t3sY/Rwaf5svb+Y59e1+z8xVxyPKg2MGMGuH5R8vZdxy7lqnpNx/7X3/AObT/wCkVYwcIYjbR6r73XP9R77NsztZUGtFTK27dlTVaSTsXKcvilxYsUISOnFGIiUGRO5f/9b0rqjQcJ85H2MNLXfaOdu1zXd/3vorIy6sxlNn2frOmNvDxbDfcSw7bsr81lGz/B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)
Development Stage
Proof of concept has been demonstrated in a laboratory setting.
Publication: VP Ma et al., (2016). Angew Chem Int Ed Engl. 55(18):5488-92.
Patent Information
App Type |
Country |
Serial No. |
Patent No. |
File Date |
Issued Date |
Patent Status |
Utility (parent) |
United States |
15/456,024 |
10,900,069 |
3/10/2017 |
1/26/2021 |
Issued |
|
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