Test yourself on the math from the lesson. There are 38 kinds of problem, from warm-ups to challenges, and each one gives you new numbers whenever you ask.
38 kinds of problem. Solve as many as you like.
1. Averages, spread and square roots
RememberA random walk adds a step of +1 or −1 at random each time. The mean of the end positions stays near 0, so it says nothing about spread. The mean square, the average of x2, does: after N steps it is N. Its square root, the root mean square (RMS), is N. With steps of length a, the typical distance after N steps is aN, and reaching a distance x takes about (x/a)2 steps.
You watch a 1-µm bead jiggle in water under a microscope. In 5 separate 1-second intervals, it moves these distances along the x axis: 0.7, −1.2, 0.8, −0.6 and −0.8 µm. What is the mean (average) displacement, in µm? Keep the signs: a minus means a move to the left.
1.2
The mean square displacement
Warm-up
5 walkers each take 36 random steps of +1 or −1, flipping a coin for each step. They end at −12, 12, −2, 0 and 4 steps from where they started. What is the mean square displacement: the average of the squared distances, in steps²?
1.3
Root mean square (RMS) distance
Warm-up
Many walkers each take 400 random steps of +1 or −1. The mean square of their end positions is 400 steps². What is the root mean square (RMS) distance from the start, in steps?
1.4
More steps, how much farther?
Warm-up
A random walker should end up typically 10 times as far from its start as before (same step length). How many times as many steps does it need?
1.5
Typical distance after N steps
Practice
In syn3A's 3D model, the cell is split into 8-nm boxes and a molecule moves by hopping from a box to a neighbor. After 100 hops, how far is a molecule typically from where it started, in nm?
1.6
How many steps to get that far?
Practice
A protein's motion is drawn as 1-nm hops in random directions. About how many hops does it take to get typically 50 nm from its start?
2. Diffusion
RememberThe diffusion coefficient D says how fast the mean square displacement grows: MSD =2dDt, with d the number of dimensions (1, 2 or 3), so MSD =6Dt in 3D. D is an area per time, such as µm²/s; 1 cm² = 108 µm² and 1 m² = 1012 µm². For a sphere of radius r in a fluid of viscosity η, Stokes–Einstein says D=kT/(6πηr), with T in kelvin and k=1.381×10−23 J/K. Water is 0.890 mPa·s at 25 °C and 0.691 mPa·s at 37 °C.
GFP in water diffuses with D = 87 µm²/s. What is its mean square displacement (MSD) after 1 ms, in 3D? Give it in µm².
2.2
Units of D
Warm-up
GFP in water diffuses with D = 87 µm²/s. An older table lists values in cm²/s. What is it in cm²/s?
2.3
D from a tracked path
Practice
In an experiment, GFP molecules in water are followed in 3D. Their mean square displacement after 1 ms is 0.53 µm². What is their diffusion coefficient D, in µm²/s?
2.4
Bigger, thicker, warmer
Practice
GFP diffuses in water with D = 87 µm²/s. For GFP, the cytoplasm of a mammalian cell behaves like a fluid 3.2 times as viscous as water (Swaminathan and colleagues, 1997). What D would you expect for GFP there, in µm²/s?
2.5
Stokes–Einstein: from size to D
Challenge
Use Stokes–Einstein, D=kT/(6πηr), for a GFP-size protein in water at 20 °C, where the viscosity is η = 1.002 mPa·s. Take r = 2.8 nm and k = 1.381×10−23 J/K. What is D, in µm²/s?
3. Why time grows with distance squared
RememberTurn MSD =6Dt around: the typical time to wander a distance x in 3D is t=x2/(6D). Along a thin tube such as an axon the motion is 1D, so t=x2/(2D). Twice as far takes four times as long. In a time t a molecule typically gets 6Dt from its start. A motor at speed v takes x/v, and the two take the same time at x=6D/v. Kinesin walks at about 0.8 µm/s in 8-nm steps, one ATP each.
A protein diffuses for 9 times as long as before. How many times as far from its start does it typically get?
3.2
Time to cross a cell
Practice
A ribosome in E. coli diffuses with D = 0.04 µm²/s. About how long does it take to wander across syn3A, about 0.4 µm? Use t=x2/(6D) and give the answer in ms.
3.3
Down an axon
Practice
A GFP-size protein in nerve cytoplasm diffuses with D = 27 µm²/s. About how long would it take to wander 1 cm along an axon, a long thin tube where it can only move along the line? Use t=x2/(2D) and give the answer in days.
3.4
How far in a given time?
Practice
A ribosome in E. coli diffuses with D = 0.04 µm²/s. How far from its start does it typically get in 1 second, in 3D? Give the answer in nm.
3.5
Motors: distance ÷ speed
Practice
A human cell is about 20 µm across. Compare two ways to move a big complex the size of a ribosome (D = 0.04 µm²/s) across it: diffusion, with t=x2/(6D), or riding a kinesin motor at 0.8 µm/s. Whichever is faster, how many times longer does the slower way take?
3.6
Where motors start to win
Challenge
Over a distance x, diffusion takes about x2/(6D) and a kinesin motor at v = 0.8 µm/s takes x/v. For GFP in mammalian cytoplasm (D = 27 µm²/s), at what distance do the two take the same time? Give it in µm.
4. A crowded cell
RememberN molecules in a volume V make a concentration N/(NAV), with V in liters: 1 µm³ = 10−15 L = 109 nm³. One molecule is about 49.6 nM in syn3A (0.0335 µm³) and 1.7 nM in E. coli (1 µm³). A sphere of radius r has volume 34πr3. N molecules spread evenly sit about (V/N)1/3 apart. One molecule finds one fixed partner, with contact distance R, in about t=V/(4πDR).
syn3A has a volume of about 0.0335 µm³. A protein is at 5 µM in it. About how many molecules of it does the cell hold?
4.2
How much room do they take?
Practice
A large syn3A cell in the same tomograms had a radius of 247 nm and held 820 ribosomes. What percent of the cell's volume do the ribosomes fill, treating each as a sphere of radius 10 nm?
4.3
How far apart are they?
Practice
syn3A (0.0335 µm³) holds about 503 ribosomes. If they were spread evenly, about how far apart would neighboring ribosomes be (center to center)? Use (V/N)1/3 and give it in nm.
4.4
Finding one partner
Challenge
One protein (D = 7.7 µm²/s) searches for one partner; they react when they touch, at a distance R = 5 nm. The mean search time in a volume V is t=V/(4πDR). In what volume would the search take 1 s on average? Give it in µm³.
5. Rates of change
RememberdA/dt is how fast A changes, per unit of time. For first-order decay, dA/dt=−kA, which gives A=A0e−kt. The rate constant comes from the half-life: k=ln2/t1/2, with ln2≈0.693. Euler's method steps forward: new = old + rate × Δt, so for decay Anew=A(1−kΔt). Halving Δt roughly halves Euler's error, and a step with kΔt>1 overshoots.
A less stable mRNA (made up) has a half-life of 2 minutes. What is the rate constant k, per minute?
5.2
How fast at the start?
Warm-up
A syn3A cell holds 500 copies of a protein and stops making new ones. They break down with k = 0.0277 per hour (a 25-hour half-life). So dA/dt=−kA. What is dA/dt at the start, in proteins per hour?
5.3
One Euler step
Warm-up
A box holds 1,000 protein complexes, which fall apart with k = 10 per second (made-up numbers). So dA/dt=−kA. Take one Euler step of Δt = 0.01 seconds. How many complexes does Euler's method predict after the step?
5.4
Several Euler steps
Practice
A syn3A cell holds 8 copies of an mRNA and stops making new ones. Each copy breaks down with k = 0.1733 per minute (a 4-minute half-life). Use Euler's method with steps of Δt = 0.5 minutes. Starting from 8, what value do you get after 4 steps (at t = 2 minutes)?
5.5
Exponential decay
Practice
A box holds 1,000 protein complexes, which fall apart with k = 0.001 per second (made-up numbers). So A(t)=A0e−kt. On average, how many complexes are left after 1,000 seconds?
5.6
How wrong is Euler's method?
Challenge
A test tube holds 100 molecules of A, which break down with k = 0.5 per second. Euler's method with steps of Δt = 1 second runs to t = 2 seconds. By how much does it fall short of the exact answer A0e−kt there?
6. Second-order reactions
RememberFor A + B → C, rate =k[A][B] in M/s, so k is in M⁻¹ s⁻¹. In a volume V (in liters), one particular A–B pair reacts at k/(NAV) per second: k×4.96×10−8 in syn3A. When B is plentiful, one A reacts at k[B] per second, and the average wait is 1 ÷ rate. If every meeting reacts, k=4π(DA+DB)(RA+RB)NA×1,000 (Smoluchowski), with D in m²/s and R in m: about 109 to 1010 M⁻¹ s⁻¹. Real protein pairs are nearer 106.
For the reaction A → B, mass action says the rate is k[A], in M/s (molar per second), with each concentration in M. The units of k are Mns−1. What is n?
6.2
Double one, double both
Warm-up
In A + B → C (rate k[A][B]), both [A] and [B] go up 10 times. How many times as fast is the reaction?
6.3
Rate = k[A][B]
Practice
A + B → C has k = 106 M⁻¹ s⁻¹. With [A] = 2 µM and [B] = 3 µM, how fast is C made? Give the rate in µM/s.
6.4
One pair of molecules in a cell
Practice
Two proteins A and B react with k = 106 M⁻¹ s⁻¹. In syn3A (volume 0.0335 µm³) there is one A and one B. On average, how long until they meet and react? Give it in s.
6.5
One molecule among many
Practice
A + B → C has k = 105 M⁻¹ s⁻¹. Think of one A molecule among 1,000 B molecules in syn3A (volume 3.35×10−17 L). On average, how long until the A reacts? Give it in ms.
6.6
The diffusion limit
Challenge
If every meeting reacts, the fastest possible rate constant is the Smoluchowski limit, k=4π(DA+DB)(RA+RB)×NA×1,000, with D in m²/s and R in m. Work it out for two GFP-size proteins in water at 37 °C, each with D = 117 µm²/s and radius 2.8 nm. Give k in M⁻¹ s⁻¹.
7. Binding
RememberFor A + B ⇌ C, the forward rate kon[A][B] equals the reverse rate koff[C] at equilibrium, so Kd=koff/kon, a concentration. The fraction bound is L/(L+Kd), where L is the free partner: half bound when L=Kd. To reach a fraction f you need L=Kdf/(1−f). A complex lasts 1/koff on average, with a half-life of ln2/koff. In syn3A one molecule is about 49.6 nM.
The pair in the Particles vs Equations simulation binds with kon = 107 M⁻¹ s⁻¹ and comes apart with koff = 10 s⁻¹. What is its dissociation constant Kd, in µM?
7.2
How long does a complex last?
Warm-up
In living E. coli, a lac repressor (LacI) stays on its DNA operator for about 5 minutes on average before it comes off (Hammar and colleagues, 2014). What koff does that mean, in s⁻¹?
7.3
Fraction bound
Practice
A cell holds 150 nM of a partner protein in all, but 50 nM of it is already tied up in complexes. Kd = 100 nM. What percent of the time is the protein bound? Use fraction bound = L/(L + Kd), where L is the free partner's concentration.
7.4
How much partner for a target?
Practice
A protein binds a partner with Kd = 1 µM. How much free partner is needed for the protein to be bound 99% of the time? Give it in µM.
7.5
Kd as molecules in syn3A
Challenge
A pair binds with Kd = 10 nM. In syn3A (volume 3.35×10−17 L), how many free copies of the partner make a concentration equal to Kd?
Mixed review
8 problems from across the lesson, in random order. Here the topic is hidden until you solve each one, so part of the job is working out which tool you need.
M1
Problem
Practice
A human cell is about 20 µm across. Compare two ways to move a protein as fast as GFP in E. coli (D = 7.7 µm²/s) across it: diffusion, with t=x2/(6D), or riding a kinesin motor at 0.8 µm/s. Whichever is faster, how many times longer does the slower way take?
M2
Problem
Practice
A small syn3A cell in a cryo-electron tomogram (Gilbert and colleagues, 2021) had a radius of 201 nm and held 503 ribosomes. What percent of the cell's volume do the ribosomes fill, treating each as a sphere of radius 10 nm?
M3
Problem
Practice
Glucose in water diffuses with D = 600 µm²/s. About how long does it take to wander across a human cell, about 20 µm? Use t=x2/(6D) and give the answer in ms.
M4
Problem
Practice
In an experiment, ribosomes in E. coli are tracked in a flat (2D) microscope image. Their mean square displacement after 5 seconds is 0.81 µm². What is their diffusion coefficient D, in µm²/s?
M5
Problem
Practice
A + B → C has k = 107 M⁻¹ s⁻¹. With [A] = 100 nM and [B] = 100 nM, how fast is C made? Give the rate in nM/s.
M6
Problem
Practice
A protein's motion is drawn as 1-nm hops in random directions. About how many hops does it take to wander typically 400 nm, the width of syn3A?
M7
Problem
Challenge
A pair binds with kon = 105 M⁻¹ s⁻¹ and koff = 0.5 s⁻¹ (made-up numbers). In syn3A (volume 3.35×10−17 L), how many free copies of the partner make a concentration equal to Kd?
M8
Problem
Challenge
If every meeting reacts, the fastest possible rate constant is the Smoluchowski limit, k=4π(DA+DB)(RA+RB)×NA×1,000, with D in m²/s and R in m. Work it out for two proteins with syn3A's model value, D = 1.0 µm²/s each, and radius 2.8 nm. Give k in M⁻¹ s⁻¹.