Date of Award

8-4-2023

Degree Type

Thesis

Degree Name

Master of Science (MS)

Department

Biomedical and Chemical Engineering

Advisor(s)

Shikha Nangia

Abstract

The lack of experimental research on a woman’s placenta due to ethical restrictions has led to little to no research on the biophysical changes at the molecular level that a woman undergoes during pregnancy. This research aims to understand biophysical changes in placental trophoblast cells that facilitate diffusion between maternal and fetal blood during the first and third trimesters. It is challenging to comprehend the function of the placental trophoblast lipid membrane in regulating molecular transport between the mother and placental trophoblast cells due to inadequate in vitro models. For this reason, we utilized recent findings on the lipid compositions of the placental trophoblast plasma membrane for the first and third trimesters to pioneer molecular-level simulation of the human placenta trophoblast membrane in the first and third trimesters. Results provided an understanding of lipids behavior between trimesters and offered insight for screening molecular transport across the placenta. Given the lipid compositions and molecular dynamics tools, the two-trimester membranes were examined and compared using a coarse-grained Martini system. Each lipid trimester composition was simulated with periodic boundary conditions in a 51 nm x 51 nm x 15 nm box. The upper and lower leaflet conditions were compared for trends within each trimester. Key observations between trimesters include a reduction in membrane thickness from the first to the third trimester, a decrease in order parameter from the first to the third trimester, an increase in area per lipid from the first trimester to the third trimester, and the difference the in the number of Chol reduction in membrane thickness from the first to the third trimester, a decrease in order parameter from the first to the third trimester, an increase in area per lipid the from the first trimester to third trimester, and the difference in the number of cholesterols between leaflets narrowed from the first to third trimester with the number of cholesterol flip flops increasing from the first to the third trimester. Observations like the reduction in thickness reflect previously presented experimental data by researchers. In summary, using molecular dynamics for placental trophoblast membranes enables us to gain insight into the placental trophoblast lipid membrane behavior from the first to the third trimester.

Access

Open Access

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