How soft is a single protein? The stress–strain curve of antibody pentamers with 5 pN and 50 pm resolutions

Abstract

Understanding the mechanical functionalities of complex biological systems requires the measurement of the mechanical compliance of their smallest components. Here, we develop a force microscopy method to quantify the softness of a single antibody pentamer by measuring the stress–strain curve with force and deformation resolutions, respectively, of 5 pN and 50 pm. The curve shows three distinctive regions. For ultrasmall compressive forces (5–75 pN), the protein's central region shows that the strain and stress are proportional (elastic regime). This region has an average Young's modulus of 2.5 MPa. For forces between 80 and 220 pN, the stress is roughly proportional to the strain with a Young's modulus of 9 MPa. Higher forces lead to irreversible deformations (plastic regime). Full elastic recovery could reach deformations amounting to 40% of the protein height. The existence of two different elastic regions is explained in terms of the structure of the antibody central region. The stress–strain curve explains the capability of the antibody to sustain multiple collisions without any loss of biological functionality.