Biological complexity: molecules fold, interpret information (Introduction)

by David Turell , Wednesday, September 02, 2020, 23:14 (1543 days ago) @ David Turell

How information and sensations are transmitted by molecules:

https://evolutionnews.org/2020/08/research-reveals-biological-design-in-the-sensing-and...

"A paper in PNAS on describes the properties of talin, “an adaptor protein that transduces mechanical signals into biochemical cues by recruiting a network of protein ligands in a force-dependent way.” This example complements our earlier article about mechanotransduction. Once again, fine tuning of forces and materials is found, but this time at a scale that is orders of magnitude smaller.

"These force cues have a complex nature, oscillate in time with different frequency components, and are often embedded in noise. However, most assays to explore the mechanics of force-sensing proteins rely on simple perturbations, such as constant or ramped forces. Here, we use our magnetic tweezers design to subject single talin domains to oscillatory forces and external mechanical noise. We show that talin ignores random external fluctuations but synchronizes its folding dynamics with force oscillations in a frequency-dependent way. We hypothesize that this finely tuned response could underpin talin force-sensing properties.

"Talin’s job as an “exquisite force sensor” is to grab and hold parts together inside the cell.

"Talin is a mechanosensing hub protein in focal adhesions, which cross-links transmembrane integrins with the active F-actin filaments and recruits several binding proteins to control the function and fate of this organelle. For example, vinculin binds to cryptic helices in mechanically unfolded talin domains, subsequently recruiting actin filaments that reinforce the cellular junction. Hence, talin transduces mechanical forces through its folding dynamics.

"This enzyme senses motions of neighboring cells or the extracellular matrix. Somehow, talin deconvolves this noisy signals of motion into recognizable oscillations at particular frequencies and knows how to respond. Its spring-like domains unfold so that other molecules can attach, and then it binds them together. It is a truly remarkable reaction that differs from other types of mechanosensing, opening the door for more discoveries in biophysics at the molecular scale:

"Although initially formulated in the context of nonlinear physics, stochastic resonance has been demonstrated in a broad range of biological systems, with particular emphasis as a sensory mechanism in mechanoreceptors, like the crayfish hair cells, the cricket cercal system, or the vestibular and auditory system. Interestingly, in all of these examples, signal transduction involves the activation of gated ion channels, which convert mechanical perturbations into electrophysiological signals. However, mechanotransduction also involves biochemical signaling, where force stimuli trigger downstream signaling pathways through a complex network of interacting proteins. In this sense, it remains to be explored whether stochastic resonance could also play a role in mechanotransduction pathways that involve ligand binding to force-bearing proteins instead of gating of mechanosensitive channels.

"In the case of talin, the implications for design are clear:

"Mechanical signal transduction relies on the robust and finely tuned response of molecular force sensors.Mechanical information is encoded in both the amplitude of the signal and its time-dependent evolution. Hence, both components must be accurately deciphered and interpreted by cellular force sensors.

"The only evolution spoken of in the paper is the “time-dependent evolution” (unfolding) of the vibrations that talin senses: i.e., the behavior of the oscillations from initiation to damping. That ability implies even more design than a simple response to a vibration. It implies that talin can recognize encoded information both in the signal strength and in its behavior in time, and respond accordingly by unfolding the appropriate domain for binding to other protein parts. The three authors from Columbia University describe the actions of this enzyme as a “tuning fork of cellular mechanotransduction.”

"No Miracles Here

"These examples of biological mastery of force are not miracles; they are subject to the laws of physics and obey the laws of physics. But wow, do they know how to take advantage of the laws of physics! From the mightiest dinosaur, to the largest birds, to the tiniest spider, to molecules in the cell, biological designs show how to push the limits of the possible. Such exceptional applications of materials and forces rightly excite our wonder and admiration."

Comment: Another entry from the ID website showing the necessity for a designer.