David Coppedge writes:
New imaging techniques down to the picometer scale are permitting the detection of previously unknown alliances of cellular software with electrostatics and mechanics. Such knowledge was unattainable until biophysicists gained the ability to measure phenomena at the atomic level. What they are finding multiplies the information content embedded in the molecules of life.
Early depictions of molecules in the nucleus showed them drifting around aimlessly. How could molecules do otherwise without membranes to hold them together? Organelles are defined by their lipid membranes. The simplified picture of molecules in lipid cages, like animals in a zoo, raised questions about how enzymes locate their substrates in regions that, at their scale, would be distant.
The Electric Cell
New findings reported in PNAS by Toyama et al. are uncovering a role for electrostatics in enzymatic activity. Simultaneously, the discovery may offer insight into the function of so-called “disordered proteins” that never fold into stable structures, and other proteins containing disordered regions that would seem to flail about like loose cables. But there is order in the disorder! How big is this discovery?
Electrostatic interactions play important roles in regulating a plethora of different biochemical processes and in providing stability to biomolecules and their complexes.
What the team from the University of Toronto found, discussed below, was only made possible by “solution NMR spectroscopy.” This technique allows them, for the first time, to measure the near-surface electrostatic potentials of individual atoms in proteins and follow changes in those potentials during an enzyme’s action.
Our results collectively show that a subtle balance between electrostatic repulsion and interchain attractive interactions regulates CAPRIN1 phase separation and provides insight into how nucleotides, such as ATP, can induce formation of and subsequently dissolve protein condensates. [Emphasis added.]
This remarkable revelation begins to give insight into the participation of cell coding with electrophysics. Get a charge out of that!
CAPRIN1 coexists with negatively charged RNA molecules in cells and, along with FMRP and other proteins, is implicated in the regulation of RNA processing and translational activity. Thus, electrostatics play a central role in modulating the biological functions of this protein, and measurement of electrostatic potentials at each site along its backbone, as reported here, provides an opportunity to understand in more detail the important role of charge in this system.
The paper only investigated one enzyme, so caution is advised before generalizing. The authors feel, though, that this electrical code model will help explain many other processes that require molecules to come together, perform their work, and then separate. It’s the new Electric Cell.
Coded Mechanics, Too
Another case of physics in cellular processing was uncovered by a team from the University of Washington who also published their work in PNAS. And once again, it was new creative imaging at the atomic scale that made the discovery possible.
This team worked on a helicase enzyme named PcrA, which unwinds DNA for transcription. This enzyme works so fast (1000 bases per second!) it’s been like trying to describe the blur of a racecar speeding down a track. Using a new technique called “single-molecule picometer-resolution nanopore tweezers” (SPRNT), they were able to slow down the action and watch the racecar move with its “inchworm mechanism” one base at a time. This blends chemistry with another branch of physics, mechanics: “mechanochemistry.”
[Design advocates] look past the magical thinking and see the operation of a designing mind with foresight and purpose, intimately familiar with the laws of physics, able to write code to utilize those laws in precision operations. Now, it becomes clear that the precision goes deeper than previously known.
The full article at Evolution News contains further details. The significant takeaway, however, is that new research is discovering profound layers of complexity in cellular function that confounds the assumption of unguided interatomic forces as responsible for life.