scholarly journals Concentration Sensing in Crowded Environments

2020 ◽  
Author(s):  
Wylie Stroberg ◽  
Santiago Schnell

ABSTRACTSignal transduction within crowded cellular compartments is essential for the physiological function of cells and organisms. While the accuracy with which receptors can probe the concentration of ligands has been thoroughly investigated in dilute systems, the effect of macromolecular crowding on the inference of concentration remains unknown. In this work we develop a novel algorithm to simulate reversible reactions between reacting Brownian particles. This facilitates the calculation of reaction rates and correlation times for ligand-receptor systems in the presence of macromolecular crowding. Using this method, we show that it is possible for crowding to increase the accuracy of estimated ligand concentration based on receptor occupancy. In particular, we find that crowding can enhance the effective association rates between small ligands and receptors to a large enough degree to overcome the increased chance of rebinding due to caging by crowding molecules. For larger ligands, crowding decreases the accuracy of the receptor’s estimate primarily by decreasing the microscopic association and dissociation rates.SIGNIFICANCEDeveloping an understanding of how cells effectively transmit signals within or between compartments under physical constraints is an important challenge for biophysics. This work investigates the effect that macromolecular crowding can have on the accuracy of a simple ligand-receptor signaling system. We show that the accuracy of an inferred ligand concentration based on the occupancy of the receptor can be enhanced by crowding under certain circumstances. Additionally, we develop a simulation algorithm that speeds the calculation of reaction rates in crowded environments and can be readily applied to other, more complex systems.

2020 ◽  
Vol 21 (16) ◽  
pp. 5908 ◽  
Author(s):  
Alain A. M. André ◽  
Evan Spruijt

Biomolecular condensates play a key role in organizing cellular fluids such as the cytoplasm and nucleoplasm. Most of these non-membranous organelles show liquid-like properties both in cells and when studied in vitro through liquid–liquid phase separation (LLPS) of purified proteins. In general, LLPS of proteins is known to be sensitive to variations in pH, temperature and ionic strength, but the role of crowding remains underappreciated. Several decades of research have shown that macromolecular crowding can have profound effects on protein interactions, folding and aggregation, and it must, by extension, also impact LLPS. However, the precise role of crowding in LLPS is far from trivial, as most condensate components have a disordered nature and exhibit multiple weak attractive interactions. Here, we discuss which factors determine the scope of LLPS in crowded environments, and we review the evidence for the impact of macromolecular crowding on phase boundaries, partitioning behavior and condensate properties. Based on a comparison of both in vivo and in vitro LLPS studies, we propose that phase separation in cells does not solely rely on attractive interactions, but shows important similarities to segregative phase separation.


Biochemistry ◽  
1990 ◽  
Vol 29 (14) ◽  
pp. 3563-3569 ◽  
Author(s):  
Christopher M. Waters ◽  
Kerby C. Oberg ◽  
Graham Carpenter ◽  
Knowles A. Overholser

2018 ◽  
Vol 10 (10) ◽  
pp. 587-597 ◽  
Author(s):  
Henrik S. Thoke ◽  
Luis A. Bagatolli ◽  
Lars F. Olsen

The kinetics of enzymes in crowded environments are described better by the Association Induction hypothesis compared to traditional steady-state kinetics.


2017 ◽  
Author(s):  
SangYoon Chung ◽  
Eitan Lerner ◽  
Yan Jin ◽  
Soohong Kim ◽  
Yazan Alhadid ◽  
...  

ABSTRACTBiological reactions in the cellular environment differ physicochemically from those performed in dilute buffer solutions due to, in part, slower diffusion of various components in the cellular milieu, increase in their chemical activities, and modulation of their binding affinities and conformational stabilities.In vivotranscription is therefore expected to be strongly influenced by the ‘crowdedness’ of the cell. Previous studies of transcription under macromolecular crowding conditions have focused mainly on multiple cycles of RNAP-Promoter associations, assuming that the association is the rate-determining step of the entire transcription process. However, recent reports demonstrated that late initiation and promoter escape could be the rate-determining steps for some promoter DNA sequences. The investigation of crowding effects on these steps undersingle-roundconditions is therefore crucial for better understanding of transcription initiationin vivo. Here, we have implemented anin vitrotranscription quenched-kinetics single-molecule assay to investigate the dependence of transcription reaction rates on the sizes and concentrations of crowders. Our results demonstrate an expected slowdown of transcription kinetics due to increased viscosity, and an unexpected enhancement in transcription kinetics by large crowding agents (at a given viscosity). More importantly, the enhancement’s dependence on crowder size significantly deviates from hard-sphere model (scaled-particle theory) predictions, commonly used for description of crowding effects. Our findings shed new light on how enzymatic reactions are affected by crowding conditions in the cellular milieu.


1993 ◽  
Vol 333 ◽  
Author(s):  
Shi-Ben Xing ◽  
Andrew C. Buechele ◽  
Ian L. Pegg

ABSTRACTExplanation of the striking non-linear effect of glass composition on the aqueous dissolution represents an important challenge to existing dissolution mechanisms. Surface layers that are formed during glass dissolution may play an important role in this effect. One chemically reactive and one less-reactive nuclear waste glass (leachate concentrations differ by about a factor of 10) were reacted in deionized water. Two types of glass powders were used: Type A powders were pristine glass powders; Type B powders were the glass powders which had been reacted for 120 days to develop the surface layers. Both the solution concentrations and the surface layers were investigated. The experimental observations indicate that: (i) There is a range of glass compositions over which small differences in composition lead to large changes in both reaction rates and surface layer thickness; and (ii) The reaction rate is strongly affected by the formation of the surface layer (the layer appears to be protective) and cannot be explained in terms of saturation effects alone. The findings are contrary to the conclusion of a previous study and serve to highlight the inadequacy of existing dissolution models predicated on an overly simplistic mechanism, especially with regard to glass composition effects.


2007 ◽  
Vol 14 (03) ◽  
pp. 419-424 ◽  
Author(s):  
VLADIMIR P. ZHDANOV

In the middle of the previous century, G. K. Boreskov, and J. Horiuti and S. Enomoto independently showed that for reversible reactions, running via a one-route mechanism with a rate-limiting step, there exist general relationships between the reaction rates in the forward and backward directions and also between the corresponding apparent activation energies and reaction heat. Their treatments are formally applicable to gas- and liquid-phase reactions and also to heterogeneous catalytic reactions (HCR) occurring in an ideal overlayer adsorbed on a uniform surface. In reality, HCR often run on heterogeneous surfaces, and the HCR kinetics are complicated by adsorbate–adsorbate lateral interactions. I explicitly demonstrate that in such situations the Boreskov–Horiuti–Enomoto rules are applicable as well.


Author(s):  
V. Annamalai ◽  
L.E. Murr

Economical recovery of copper metal from leach liquors has been carried out by the simple process of cementing copper onto a suitable substrate metal, such as scrap-iron, since the 16th century. The process has, however, a major drawback of consuming more iron than stoichiometrically needed by the reaction.Therefore, many research groups started looking into the process more closely. Though it is accepted that the structural characteristics of the resultant copper deposit cause changes in reaction rates for various experimental conditions, not many systems have been systematically investigated. This paper examines the deposit structures and the kinetic data, and explains the correlations between them.A simple cementation cell along with rotating discs of pure iron (99.9%) were employed in this study to obtain the kinetic results The resultant copper deposits were studied in a Hitachi Perkin-Elmer HHS-2R scanning electron microscope operated at 25kV in the secondary electron emission mode.


1998 ◽  
Vol 77 (5) ◽  
pp. 1277-1281
Author(s):  
Alexander M. Berezhkovskii, Veaceslav Zaloj,

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