{"id":3690,"date":"2011-07-11T15:33:25","date_gmt":"2011-07-11T15:33:25","guid":{"rendered":"https:\/\/mtlsites.mit.edu\/annual_reports\/2011\/?p=3690"},"modified":"2011-07-19T20:55:03","modified_gmt":"2011-07-19T20:55:03","slug":"micropatterning-of-cells-to-study-autocrine-signaling-2","status":"publish","type":"post","link":"https:\/\/mtlsites.mit.edu\/annual_reports\/2011\/micropatterning-of-cells-to-study-autocrine-signaling-2\/","title":{"rendered":"Micropatterning of Cells to Study Autocrine Signaling"},"content":{"rendered":"

Autocrine signaling is a mode of chemical signaling that occurs when cells can capture self-secreted diffusive factors.\u00a0 Apart from its major role in sustaining cancer growth, autocrine signaling is also involved in the positive-feedback regulation of various physiological processes.\u00a0 Due to the closed-loop nature and complex interplay of this signaling with other signaling cues, it is difficult to validate the presence and function of autocrine loops.\u00a0 Studying these loops typically requires the use of specific inhibitors to perturb the underlying ligand\/receptor pairing, limiting investigation of poorly characterized autocrine loops.<\/p>\n

To promote the examination of autocrine signaling in broader biological systems, we have developed a general method for modulating autocrine activity using cell patterning.\u00a0 In addition to capturing self-secreted ligands, cells with autocrine loops also acquire ligands from their neighbors.\u00a0 By modulating the relative positioning between cells, we are able to modulate capture of autocrine ligands without needing specific inhibitors.\u00a0 In particular, we use stencil cell patterning to organize cells as square-latticed arrays of circular patches of varying array spacing (Figures 1A & B).\u00a0 We found that the cell-patterning platform can maintain uniform local cell density at all array spacings, in contrast to randomly plated cells, which exhibit increasing local cell density (Figure 1C). \u00a0By reducing the influence of these other environmental cues, we are able to more explicitly study the effect of autocrine signaling on cell phenotype.<\/p>\n

In addition to studying the direct role of autocrine signaling, the cell-patterning platform can also be used to investigate the interplay of autocrine signaling with other signaling cues and to evaluate its contribution towards cell-to-cell variability.\u00a0 To determine the concurrent role of cell-cell contacts, we can compare cell responses between single patches and multiple patches where the cell number of both designs is equal (Figures 2A & B). To evaluate the contribution of autocrine loops in causing cell-to-cell variability, we can determine how the inclusion of a large cell patch will perturb the response of an array of small patches (Figure 2C).\u00a0 These innovative cell-patterning designs provide us novel tools for characterizing the impact of autocrine signaling without prior knowledge of the underlying ligand\/receptor interactions.<\/p>\n\n\t\t