Molecular Dynamics Simulations Indicate that Deoxyhemoglobin, Oxyhemoglobin, Carboxyhemoglobin, and Glycated Hemoglobin under Compression and Shear Exhibit an Anisotropic Mechanical Behavior

TL;DR

This study uses steered molecular dynamics simulations to reveal that different hemoglobin forms exhibit anisotropic mechanical behavior under compression and shear, with glycated hemoglobin showing higher stiffness than other forms.

Contribution

The paper introduces a novel molecular dynamics approach to analyze the anisotropic mechanical properties of various hemoglobin structures under mechanical loading.

Findings

Glycated hemoglobin has higher stiffness than other forms.

Hemoglobin exhibits anisotropic mechanical behavior.

Structural differences influence mechanical strength.

Abstract

We developed a new mechanical model for determining the compression and shear mechanical behavior of four different hemoglobin structures. Previous studies on hemoglobin structures have focused primarily on overall mechanical behavior; however, this study investigates the mechanical behavior of hemoglobin, a major constituent of red blood cells (RBCs), using steered molecular dynamics (SMD) simulations to obtain anisotropic mechanical behavior under compression and shear loading conditions. Four different configurations of hemoglobin molecules were considered: deoxyhemoglobin (deoxyHb), oxyhemoglobin (HbO2), carboxyhemoglobin (HbCO), and glycated hemoglobin (HbA1C). The SMD simulations were performed on the hemoglobin variants to estimate their unidirectional stiffness and shear stiffness. Although hemoglobin is structurally denoted as a globular protein due to its spherical shape and secondary structure, our simulation results show a significant variation in the mechanical strength in different directions (anisotropy) and also a strength variation among the four different hemoglobin configurations studied. The glycated hemoglobin molecule possesses an overall higher compressive mechanical stiffness and shear stiffness when compared to deoxyhemoglobin, oxyhemoglobin, and carboxyhemoglobin molecules. Further results from the models indicate that the hemoglobin structures studied possess a soft outer shell and a stiff core based on stiffness.