We investigated the influences of molecular crowding on biochemical reaction processes on two-dimensional surfaces, using the model of signal-transduction processes on biomembranes. We performed simulations of the two-dimensional cell-based model, which describes the reactions and diffusions of the receptors, signaling proteins, target proteins , and crowders , on the cell membrane. The signaling proteins are activated by receptors and induce target proteins to unbind from the membrane. We found that the reaction rates of two-dimensional systems consistently exhibit a maximum at a high volume fraction of molecules , such that two molecules in the vicinity cannot easily exchange their positions . We further demonstrated that molecular crowding influences the hierarchical molecular distributions throughout the reaction process. The signaling proteins tend to surround the receptors, and the target proteins tend to become distributed around the signaling protein-receptor clusters. This distribution accelerates the receptor--signaling protein and signaling protein-target protein reactions. Thus, molecular crowding frequently enhances reactions on two-dimensional surfaces, but restricts reactions in three-dimensional bulk systems .
We investigated the influences of the excluded volume of molecules on biochemical reaction processes on two-dimensional surfaces, using the model of signal-transduction processes on biomembranes. We performed simulations of the two-dimensional cell-based model, which describes the reactions and diffusion of the receptors, signaling proteins, target proteins and crowders on the cell membrane. Here, the signaling proteins are activated by receptors and these activated signaling proteins activate target proteins, causing that to unbind from the membrane. We found that the signal flow of the system, defined as the activation rate of target protein, shows the following non-trivial variations against the change in the volume fraction of molecules or the affinity of the target protein to the membrane. For example, with an increase in the binding rate of target proteins to the membrane, the signal flow varies in the form i) monotonically increasing, ii) increasing then decreasing in a bell-shaped curve, or iii) increasing, decreasing then, increasing in an S-shaped curve . We further demonstrated that the excluded volume of molecules influences the hierarchical molecular distributions throughout the reaction processes. In particular, when the system exhibits large signal flow, the signaling proteins tend to surround the receptors, and the target proteins tend to become distributed around the receptor--signaling protein clusters. This accelerates both types of reactions. To explain these phenomena, we analyzed the stochastic model of the local motions of molecules around the receptor .
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molecular crowding
the excluded volume of molecules
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diffusions
diffusion
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, and crowders ,
and crowders
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The
Here, the
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induce target proteins
these activated signaling proteins activate target proteins, causing that
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reaction rates of two-dimensional systems consistently exhibit a maximum at a high
signal flow of the system, defined as the activation rate of target protein, shows the following non-trivial variations against the change in the
R
, such that two molecules in the vicinity cannot easily exchange their positions
or the affinity of the target protein to the membrane. For example, with an increase in the binding rate of target proteins to the membrane, the signal flow varies in the form i) monotonically increasing, ii) increasing then decreasing in a bell-shaped curve, or iii) increasing, decreasing then, increasing in an S-shaped curve
R
molecular crowding
the excluded volume of molecules
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process. The
processes. In particular, when the system exhibits large signal flow, the
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signaling protein-receptor
receptor--signaling protein
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distribution accelerates the receptor--signaling protein and signaling protein-target protein reactions. Thus, molecular crowding frequently enhances reactions on two-dimensional surfaces, but restricts reactions in three-dimensional bulk systems
accelerates both types of reactions. To explain these phenomena, we analyzed the stochastic model of the local motions of molecules around the receptor