• Home
  • Textbooks
  • Physical Biology of the Cell
  • Rate Equations and Dynamics in the Cell

Physical Biology of the Cell

Rob Phillips, Jane Kondev, Julie Theriot

Chapter 15

Rate Equations and Dynamics in the Cell - all with Video Answers

Educators


Chapter Questions

02:50

Problem 1

Consider the measurements shown in Figure 15.4 where global and local concentrations of various cytoskeletal proteins in fission yeast cells were determined using fluorescence microscopy. Here we make use of the measured concentrations, reported in Table 1 of $\mathrm{Wu}$ and Pollard $(2005),$ to make estimates for the fission yeast cytoskeleton.
(a) Estimate the volume of a fission yeast cell. Next, given the concentration of actin monomers, capping proteins, and formins, work out the mean spacing between these proteins. Then, use your estimated volume and the measured concentrations to estimate the number of copies of each of these proteins in the "typical" fission yeast cell.
(b) About half of the actin monomers in the yeast cell are in filamentous form at any given time. Given the dissociation constant for capping proteins, $K_{\mathrm{d}}=1 \mathrm{nM}$, estimate the average length of actin filaments, assuming one capping protein per filament. Compare your estimate with the typical value, which is of the order of 100 monomers per filament.

Norman Atentar
Norman Atentar
Numerade Educator
03:24

Problem 2

In Equation $15.22,$ we described the kinetics of an isomerization reaction. Here we do the math and explore a couple of examples of this reaction.
(a) Work out the solution for the concentrations of both species and make plots of $c_{\mathrm{A}}(t), c_{\mathrm{B}}(t),$ and their sum. Assume that initially there are only molecules of species $A$ present, at concentration $c_{0}.$
(b) Apply the results of (a) to the decay of 13 -cis-retinal to all-trans-retinal, as was illustrated in Figure $15.8 .$ The half-life of this reaction is $\tau=2 \mathrm{s}.$
(c) At a very different time scale, these same ideas apply to radiometric dating. A celebrated example is the decay of potassium to argon with a half-life of 1.26 billion years. Plot the amount of argon as a function of time, assuming initially only potassium is present.

Banhishikha Sinha
Banhishikha Sinha
Numerade Educator
01:06

Problem 3

Rate equations for interconversion
Consider the reversible reaction
\[
A \rightleftharpoons B
\]
In this case, the rate equations of interest can be written as
\[
\frac{\mathrm{d} c_{\mathrm{A}}}{\mathrm{d} t}=-k_{+} c_{\mathrm{A}}+k_{-} c_{\mathrm{B}}
\]
and
\[
\frac{\mathrm{d} c_{\mathrm{B}}}{\mathrm{d} t}=-\frac{\mathrm{d} c_{\mathrm{A}}}{\mathrm{d} t}
\]
with the constraint of mass conservation of the form given in Equation $15.21 .$ In this case, the long-time behavior is nonzero concentrations of both $\mathrm{A}$ and $\mathrm{B}$.
(a) Solve these equations for $c_{\mathrm{A}}(t)$ and $c_{\mathrm{B}}(t)$ assuming that only the molecular species $A$ is present at time $t=0 .$ Make plots of the solutions and demonstrate that the long-time behavior is dictated by the ratio $k_{+} / k_{-}$
(b) Using the current recording for a single sodium ion channel shown in Figure $7.2(\mathrm{A})(\mathrm{p} .283),$ estimate the opening and the closing rate of the channel. Use the result from (a) to plot the probability that the channel is open and the probability it is closed as a function of time. Assume the channel to be closed initially.

Kratika Bhadauria
Kratika Bhadauria
Numerade Educator
01:21

Problem 4

Fill in all of the details in the derivation of Equation 15.32 for the bimolecular reaction rate, given in Section 15.2 .4.

Adriano Chikande
Adriano Chikande
Numerade Educator
02:33

Problem 5

Write the full set of rate equations for the reaction described by the Michaelis-Menten kinetic model. Introduce dimensionless variables by measuring time in units of $\left(k_{-}+r\right)^{-1}$ and concentrations in units of $K_{\mathrm{m}}=\left(k_{-}+r\right) / k_{+}$ and define $\varepsilon=r /\left(r+k_{-}\right).$
(a) Solve these equations numerically and reproduce Figure $15.16(\mathrm{A})$
(b) Make a plot of $\mathrm{d}[\mathrm{P}] / \mathrm{d} t$ versus $[\mathrm{S}]$ using both the Michaelis-Menten form and the exact solution for the following choices of parameters:
(i) $[\mathrm{S}]_{0}=100,[\mathrm{E}]_{0}=1$
$\varepsilon=0.1$ and (ii) $[\mathrm{S}]_{0}=1,[\mathrm{E}]_{0}=1, \varepsilon=1 .$ What conclusion do you draw about the validity of the Michaelis-Menten form?

Adriano Chikande
Adriano Chikande
Numerade Educator
02:14

Problem 6

In this problem, we consider a phenomenological model for steady state microtubule dynamics that was introduced by Dogterom and Leibler (1993). Note that there is a more interesting class of models that include GTP hydrolysis explicitly (see Flyvbjerg et al. 1996 ). The goal of such models is to respond to data such as those in Figure 15.34 This figure shows a record of the length of a single microtubule as a function of time and reveals the series of "catastrophes" and "rescues" as the polymer changes its length.
(a) Deduce the following equations for the probability distributions $p_{+}(n, t)$ and $p_{-}(n, t),$ which give the probability of finding a microtubule:
\[
\begin{array}{l}
\frac{\partial p_{+}}{\partial t}=-f_{+-} p_{+}+f_{-+} p_{-}-v_{+} \frac{\partial p_{+}}{\partial z} \\
\frac{\partial p_{-}}{\partial t}=+f_{+-} p_{+}-f_{-+} p_{-}+v_{-} \frac{\partial p_{-}}{\partial z}
\end{array}
\]
Write a master equation for $p_{+}(n, t)$ and $p_{-}(n, t)$ by noting that there are four processes that can change the probability at each instant. Consider the $+$ case: (i) the $n-1$ polymer can grow and become an $n$ polymer, characterized by a rate $v_{+} ;$ (ii) the $n$ polymer can grow and become an $n+1$ polymer, also characterized by a rate $v_{+} ;$ (iii) the $n+$ polymer can switch from growing to shrinking with a rate $f_{+-} ;$ and (iv) the $n-$ polymer can switch from shrinking to growing with a rate $f_{-+} .$ If you account for all four of these possibilities, you will have the correct master equation. Use a Taylor expansion on factors like $p_{+}(n-1, t)-p_{+}(n, t)$ to obtain Equations 15.124 and 15.125
(b) Solve these equations for $p_{\pm}(n)$ in the steady state (that is, $\partial p_{\pm}(n, t) / \partial t=0$ ). Show that in the steady state, the probabilities $p_{\pm}(n)$ decay exponentially with constant
\[
\sigma=\frac{v_{+} f_{-+}-v_{-} f_{+-}}{v_{+} v_{-}}
\]
(c) Use Figure 15.34 to estimate the parameters $v_{+}, v_{-}, f_{+-}, f_{-+},$ and then find the average length of the polymers that is predicted by this simple model. To find the average length, you will need to sum over all lengths with their appropriate probability. The slopes of the growth and decay regions tell you about the on and off rates, and the durations of the growth and decay periods tell you something about the parameters $f_{+-}$ and $f_{-+} .$ Note that by fitting the dynamical data, you are deducing/predicting something about the distribution of lengths.

Sana Riaz
Sana Riaz
Numerade Educator
03:42

Problem 7

In the chapter, we examined the equilibrium polymer and found that it is characterized by a broad, exponential distribution of lengths. Contrary to this observation, cytoskeleton filaments in cells often have well-defined lengths that appear to be properly adjusted to their cellular function. How length control is achieved is an interesting problem, since the building blocks of cytoskeletal filaments and their interactions take place at the nanometer scale, yet they assemble into structures whose length is on the micron scale. It has been hypothesized that the cell needs to set up some sort of mechanism by which length is measured. One such mechanism was proposed for microtubule length control whereby the kinesin Kip3 walks toward the plus end of a microtubule and once there leads to depolymerization of the terminal tubulin dimers as depicted in Figure $15.38(\mathrm{A})$
In this problem, we examine a toy model of this mechanism and show that it leads to a steady-state length for microtubules. The model assumes that Kip3 molecules in solution bind to the filament monomers represented as blocks in Figure $15.38(\mathrm{B})$ with rate $k_{\text {bind }},$ and then proceed to step toward the plus end of the filament with rate $v$. Only at the end of the filament do the Kip3 molecules fall off taking a monomer block along with them. This depolymerization process competes with monomer attachment at the plus end with rate $k_{\mathrm{on}}$
(a) Show that the model predicts a steady-state occupation of the filament by Kip3 molecules such that the number of Kip3 molecules per monomer increases linearly with position toward the plus end. This is observed in experiments. For example, see Figure $3(\mathrm{b})$ in Varga et al. (2006)
(b) Compute the rate of monomer detachment at the plus end in steady state assuming that it is equal to the flux of Kip3 molecules into the terminal monomer. Compare your result with the data shown in Figure $15.38(\mathrm{C})$ and estimate the rate $k_{\text {bind }}$ for different Kip3 concentrations from the plots. Explore the dependence of $k_{\text {bind }}$ on Kip3 concentration. What do you conclude?
(c) Write down the equation for $L(t),$ the filament length as a function of time, by considering polymerization at the plus end and the length-dependent depolymerization, which we derived in the previous part. Determine the steady-state length of the microtubule at 3 nM Kip3 concentration typical of a cell, assuming a typical attachment rate of $k_{\mathrm{on}}=1 \mu \mathrm{m} / \mathrm{min} .$ (Problem courtesy of Justin Bois.)

Sana Riaz
Sana Riaz
Numerade Educator