Understanding the biophysical embryo-uterine interactions during implantation

The proposed research aims to understand biophysical embryo-uterine interactions during peri-implantation to identify factors that guide processes such as embryo orientation, egg cylinder morphogenesis, and embryonic axis formation.

Recent studies on implantation have gone beyond the traditional biochemical approach to reveal that mechanical interactions at the embryo-uterine interface are abundant and indispensable for proper implantation and development.

Due to difficulties in recreating embryo implantation ex-vivo setups and lack of in-utero accessibility, the physical forces and mechano-chemical feedbacks involved in embryo implantation, however, still remain unknown.

In this proposal, I will study how mechanical interactions at the embryo-uterine interface during implantation affect embryo development by directly measuring physical force at the interface, identifying the role of major mechanotransducer pathways, and making in-utero observations.

In Objective 1, I will build an experimental setup with 2D polyacrylamide (PAA) gels of varying mechanical properties to recapitulate the characteristics of the uterine surface in ex-vivo setups and observe how embryo development depends on the mechanical properties of the substrate.

In Objective 2, I will combine traction force microscopy (TFM) and live imaging to quantify how physical forces affect molecular and cellular events during the mouse implantation process.

In Objective 3, I will identify how the mechanical forces are transduced into biochemical cues through live-imaging and genetic/pharmaceutical perturbations.

Finally, I will investigate the implantation process live in-utero using multiphoton intravital imaging to validate my findings from ex-vivo studies.

I hypothesize that mechanical cues will be spatiotemporally linked with biochemical signaling to significantly affect embryo development.